Welcome to our 2023 recap of the latest findings on myeloma treatments reported at the American Society of Hematology (ASH) meeting that kicked off Saturday in San Diego. Highlights from today included real-world data on the use of the bispecific antibody Tecvayli, health-related quality of life findings with the CAR T-cell therapy Abecma, the use of minimum residual disease negativity, iberdomide maintenance therapy, and updates on the treatment of high-risk newly diagnosed disease and smoldering myeloma.

Relapsed/Refractory Multiple Myeloma

Tecvayli (Teclistamab)

Tecvayli (Teclistamab) was the first “off-the shelf” BCMA-targeted bispecific antibody approved for patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM; that is patients who have received 4 or more lines of therapy), including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody. In this Abstract 91, Dr. Danai Dima and colleagues from the Cleveland Clinic reported that treatment with Tecvayli in a real-world setting showed similar responses to the previously reported data from the MajesTEC-1 clinical trial without any new side effects.

Of the 102 patients with RRMM included in Dr. Dima’s analysis, 25% were non-Hispanic Black, 44% had extramedullary disease (EMD; that is, myeloma cells that are growing outside of the bone marrow) and more than 80% (83/102) would not have met the MajesTEC-1 eligibility criteria.  Their findings showed:

The authors note that results from the real-world study of the safety and efficacy of Tecvayli were like previously reported data from the MajesTEC-1 clinical trials; however, complete response (CR) rates were lower.  The lower CR rates may be due to the fact that a majority of patients evaluated did not meet the eligibility criteria MajestTEC-1 trial population; due to stringent eligibility criteria, patients in clinical trials tend to be less sick and/or have fewer comorbidities than real-world patient population, so outcomes are typically better in clinical trials. Low blood cell counts and infections remain a challenge, thus, close monitoring, supportive care and other measures are important to help patients continue with therapy.

Abecma (idecabtagene vicleucel)

Dr. Michel Delforge and colleagues in Belgium reported findings from a preliminary analysis (Abstract 96) that showed the chimeric antigen receptor T cell (CAR T-cell) therapy Abecma (idecabtagene vicleucel) significantly improved health-related quality of life when compared to standard regimens [that is, Darzalex (dara, daratumumab), Pomalyst (pomalidomide), and dexamethasone; Darzalex, Velcade (bortezomib), and dexamethasone; Ninlaro (ixazomib), Revlimid, and dexamethasone; Kyprolis (carfilzomib) and dexamethasone; or Empliciti (elotuzuamb), Pomalyst, and dexamethasone].

Researchers evaluated data from patient-reported outcomes that were collected as part of the KarMMa-3 trial.  In the phase 3 trial, Abecma significantly improved progression-free survival (PFS) and treatment response rates as compared with standard regimens, in patients with triple-class exposed (TCE) RRMM who had received 2–4 prior regimens (Rodriguez-Otero P, et al. N Engl J Med 2023).

Health-related quality of life captures information on the physical and mental health status of individuals, and on the impact of disease and treatment on a patient’s quality of life. The results from the patient-reported outcomes showed statistically significant and clinically meaningful improvements in health-related quality of life including cognitive functioning, fatigue, and pain reduction for patients with RRMM who received Abecma compared with standard treatment regimens. The authors noted that health-related quality of life improvements occurred earlier with Abecma therapy than with standard regimens, starting at approximately 2-3 months following infusion and were sustained for more than 2 years.

Minimum Residual Disease

A couple of abstracts evaluated the role of minimal residual disease (MRD) as a tool to measure the success of therapy.  MRD is an important topic in the field of multiple myeloma, in large part because we have very active treatment regimens that can bring deep and sustained responses to patients, something that was not possible just several years ago. Measuring MRD refers to counting the number of multiple myeloma cells that remain in a patient after a course of therapy is completed. For some patients, achieving MRD negativity (that is, no disease was detected after treatment) is associated with a significantly longer time before disease progression (progression-free survival [PFS]) and overall survival; however, to date, there has been limited information about its clinical meaning in patients treated with CAR T-cell therapy.

In the first presentation, (Abstract 94), Dr. Aintzane Zabaleta and colleagues from Spain found that achieving sustained MRD negativity resulted in significantly prolonged survival of RRMM patients treated with newer immunotherapies such as CAR T-cell therapy and bispecific antibodies (also known as T-cell engagers). The researchers reported that MRD negativity was associated with 88% reduction in the risk of progression and/or death. MRD negative rates were significantly higher in patients treated with CAR T-cell therapy (78%) than bispecific antibody therapy (35%).

In the next abstract, Nizar Bahlis, MD and colleagues from Canada reported (Abstract 338) that Venetoclax (Ven) combined with daratumumab (D) and dexamethasone (d) [VenDd] showed higher rates of MRD-negativity and sustained MRD-negativity compared to bortezomib plus Dd (DVd) in patients with t(11;14)-positive RRMM.

Venetoclax is a potent and selective oral BCL-2 inhibitor with demonstrated anti-myeloma activity in patients with t(11;14)-positive RRMM. The combination of VenDd has shown a high overall response rate and tolerable safety profile in the early phase study. The results in 81 patients showed:

The authors concluded that VenDd treatment showed higher rates of MRD-negativity and sustained MRD-negativity compared to DVd in patients with t(11;14)-positive RRMM.

Iberdomide Maintenance Therapy

Maintenance therapy with Revlimid (lenalidomide) is the standard of care following induction therapy and ASCT; however, all patients are at risk of relapse following transplantation, and up to 30% stop Revlimid maintenance therapy due to intolerable side effects. Thus, new treatment options with improved activity and tolerability are needed for maintenance therapy.

Iberdomide is a novel, potent oral cereblon E3 ligase modulator (CELMoD™), which is similar to but more potent than Revlimid, with a dual function: activate the immune system and directly kill myeloma cells by inducing the destruction of proteins that drive cancer growth.  Researchers from the Netherlands reported (Abstract 208) that iberdomide maintenance therapy following ASCT showed an improvement in response over time in patients who received IMiD/PI-based induction with or without anti-CD38 antibody therapy and ASCT.  Researchers noted that:

The most common serious side effects observed with iberdomide were low blood cell counts, infections, and fatigue.

The researchers conclude that iberdomide represents a novel effective post-ASCT maintenance strategy with a favorable safety profile and superior response improvement at 6 months than what has been observed with Revlimid maintenance. Iberdomide is currently being studied (versus Revlimid) as maintenance therapy following ASCT in a phase 3 trial.

Smoldering Multiple Myeloma

While observation is considered standard of care for smoldering multiple myeloma (SMM) patients who have been identified as having a high risk of progressing to active myeloma, therapeutic intervention at the SMM stage may help delay the progression to MM.

Dr. Ola Landgren, and colleagues from the University of Miami presented the final analysis of the phase 2 CENTAURUS study that showed Darzalex monotherapy demonstrated clinical activity in 123 patients with Intermediate-Risk or High-Risk SMM after a median follow-up of approximately 7 years (Abstract 210).

The researchers examined 3 different dosing schedules (that is, long intense; intermediate; short intense) to determine the optimal schedule of treatment administration for the phase 3 AQUILA study.  At a median follow up of 85 months, the study found:

The researchers conclude that this final analysis of CENTAURUS continue to demonstrate the clinical activity of DARA monotherapy in patients with intermediate- or high-risk SMM after a median follow-up of about 7 years, which supports the ongoing phase 3 AQUILA study and future SMM trials.

Data presented at the International Myeloma Society (IMS) annual meeting held September 27–30 in Athens, Greece, focused on 3 main topics: (1) the use of newer agents, (2) optimizing outcomes, and (3) the use of minimal residual disease (MRD) measurements to predict long-term outcome for patients or to potentially stop maintenance therapy.

Minimal Residual Disease (MRD)

Sustained MRD After Lenalidomide Discontinuation

Patients achieving sustained MRD negativity at 3 years post-maintenance initiation may be able to discontinue lenalidomide maintenance, according to data presented at IMS. The study enrolled 151 NDMM patients who underwent ASCT, with 42 patients successfully discontinuing lenalidomide maintenance after 3 years of sustained MRD negativity. The researchers found that MRD negativity was maintained in most patients at various time points post-discontinuation. Six months after discontinuation of lenalidomide maintenance, 39 out of 41 patients were MRD negative. At 12 months, 36 out of 38 patients continued to be MRD negative. At 18 months, all evaluable patients (n=18) remained MRD negative. At 24 months, 13 out of 14 patients were MRD negative, and at 30 months all 4 evaluable patients were MRD negative. Overall, 5 patients restarted treatment with lenalidomide monotherapy after converting from MRD negative to MRD positive following the initial completion of maintenance. One patient progressed and received second-line treatment. “Sustained MRD negativity after 3 years of lenalidomide maintenance may guide the safe discontinuation of maintenance, though this has to be proven in prospective randomized clinical trials,” the researchers note.

Predictive Model Involving MRD

A predictive model involving 3 measurable risk factors in MM—ISS stage, circulating tumor cell (CTC) levels, and time to first MRD negativity—may help identify TE patients with risk factors that can predict disease recurrence. A total of 267 patients out of 458 who attained MRD negativity by next-generation flow cytometry were analyzed over a median follow-up of 73 months. The patients in this analysis had been enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials. Results showed that 54% of patients maintained MRD negativity, 42% experienced MRD resurgence or progressive disease, and 4% died without progression. Prognostic factors at diagnosis, including ISS stage III and ≥0.01% CTCs, were found to predict MRD resurgence or progression, whereas patients achieving MRD negativity sooner, particularly after induction (<6 months), exhibited a lower risk of MRD resurgence or progression. A dynamic model incorporating ISS stage, CTC levels, and time to first MRD negativity assessment demonstrated predictive potential. Five-year rates of MRD resurgence or progression in patients with no, one, or ≥2 risk factors were 16%, 33%, and 57%, respectively. According to the researchers, this model could aid in both clinical trial design and routine practice decision-making.

Serial MRD Testing in Early Myeloma

Serial MRD testing within the first 5 years after diagnosis may help predict long-term outcomes. Data presented at IMS included 1,744 NDMM patients who underwent single or tandem ASCT. Patients were categorized into 3 groups based on their MRD test results in the initial 5 years of treatment. Group 1, which included patients with 3 serial MRD-negative tests, demonstrated an encouraging long-term outcome, with a 10-year PFS of 74%. By contrast, Group 2 included patients with both negative and positive MRD tests and exhibited a 10-year PFS of 30%. Group 3, with consistent MRD-positive tests, had a 10-year PFS of 1%. This study suggests that achieving and maintaining serial MRD negativity in the early years of myeloma treatment may predict excellent long-term outcomes, offering potential guidance for clinical practice and trials. According to the researchers, “achievement of 3 serial MRD-negative tests in the first 5 years of therapy is predictive of an excellent long-term outcome with few treatment failures.”


Jointly provided by the MMRF and RedMedEd.

This educational activity is supported by educational grants from AbbVie Inc., Bristol Myers Squibb, and GSK, and sponsorship from Legend Biotech USA Inc.

Data presented at the International Myeloma Society (IMS) annual meeting held September 27–30 in Athens, Greece, focused on 3 main topics: (1) the use of newer agents, (2) optimizing outcomes, and (3) the use of minimal residual disease (MRD) measurements to predict long-term outcome for patients or to potentially stop maintenance therapy.

Optimizing Outcomes

Zoledronic Acid, 4 Years vs 2 Years

In a study evaluating 2 vs 4 years of monthly intravenous ZOL, 192 symptomatic NDMM patients were randomized after 2 years ZOL to either 2 additional years of monthly IV ZOL or observation. The 2 additional years of ZOL were significantly superior in protecting against progressive bone disease (PBD): 8 cases were reported in the ZOL arm and 18 cases in the observational arm (HR: 0.38, 95% CI [0.17-0.88], P=0.024). In addition, there was no statistically significant difference in either osteonecrosis of the jaw (ONJ) incidence or OS between the 2 groups. According to the researchers, 79% of patients had bone involvement at diagnosis and 59% experienced bone pain. ZOL may help prevent PBD but is associated with ONJ, particularly when administered over a longer duration or with greater potency.

Pomalidomide Addition To Vd: Final OPTIMISMM Results

The final OS analysis of the OPTIMISMM trial comparing PVd vs Vd alone in patients with lenalidomide-refractory RRMM was reported. This randomized open-label phase 3 trial showed a nonsignificant trend towards improved OS with PVd (35.6 vs 31.6 months, respectively). During the study, 71% vs 70% died in the PVd and Vd groups, respectively. However, PFS was significantly improved with PVd versus Vd (22.1 vs 16.9 months; HR [95% CI], 0.77 [0.64–0.94]; P=.008). Time to treatment failure was also longer with PVd versus Vd (8.8 vs 4.6 months). The most common TEAEs with PVd were neutropenia (54%), peripheral sensory neuropathy (48%), and thrombocytopenia (40%); with Vd, the most common TEAEs were thrombocytopenia (39%), peripheral sensory neuropathy (38%), and diarrhea (31%). Peripheral neuropathy was the most common TEAE that resulted in discontinuation (PVd, 11%; Vd, 8%). According to the researchers, these data support the use of PVd as an effective treatment option in patients with RRMM.

Quadruplet Therapy in High-Risk Disease

The GMMG-CONCEPT trial evaluated the quadruplet isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in both transplant-eligible (TE) and ineligible (TNE) patients with newly diagnosed high-risk MM (HRMM), defined International Staging System (ISS) stage 2 or 3 and HRCA such as del17p, t(4;14), t(14;16), or >3 copies 1q21 (amp1q21). Results presented at IMS indicated substantial MRD negativity after consolidation, with rates of 67.7% for TE patients and 54.2% for TNE patients. The current analysis includes 127 TE and 26 TNE patients with sustained MRD negativity and PFS. After a median follow-up of 40 months for TE patients and 33 months for TNE patients, the median PFS had not yet been reached in either study arm. Exploratory analyses revealed promising 1-year and 2-year PFS rates for both groups. Additional subgroup analyses showed that patients with elevated lactate dehydrogenase (LDH) or ≥2 HRCAs or del17p were least likely to reach MRD negativity and had shortened PFS. The researchers reported that Isa-KRd induces high rates of sustained MRD negativity in newly diagnosed HRMM, translating to a median PFS that was not yet reached. The results of this study are now published and can be found here.


Jointly provided by the MMRF and RedMedEd.

This educational activity is supported by educational grants from AbbVie Inc., Bristol Myers Squibb, and GSK, and sponsorship from Legend Biotech USA Inc.

Data presented at the International Myeloma Society (IMS) annual meeting held September 27–30 in Athens, Greece, focused on 3 main topics: (1) the use of newer agents, (2) optimizing outcomes, and (3) the use of minimal residual disease (MRD) measurements to predict long-term outcome for patients or to potentially stop maintenance therapy.

Newer Agents

Novel Cereblon E3 Ligase Modulators (CELMoDs)

Iberdomide in Newly Diagnosed MM

CC-220-MM-001 is an ongoing phase 1/2 trial of iberdomide, used alone and in various combinations, in patients with both relapsed/refractory (RRMM) and newly diagnosed (NDMM) multiple myeloma. Iberdomide-dexamethasone in RRMM, as published here, showed clinical activity in heavily pretreated patients, including those with immunomodulatory-refractory disease.

The initial results of iberdomide, bortezomib, and dexamethasone (IberVd) in 18 transplant-ineligible NDMM patients demonstrated an 88.9% (95% CI, 65.3-98.6) overall response rate (ORR) in the intent-to-treat population, with 4 stringent complete responses (sCRs), 5 CRs, 5 very good partial responses (VGPR), and 2 partial responses; 2 patients were not evaluable. Overall, 9 (50.0%) patients achieved at least a CR and 14 (77.8%) patients achieved a VGPR or better. Grade 3/4 treatment-emergent adverse events (TEAEs) were noted in 70.6% of patients. Neutropenia and pneumonia were the most common AEs (17% each). No patients discontinued due to AEs, however. The researchers reported that the combination showed “high efficacy with deep, ongoing responses in this cohort of mostly older patients… supporting further assessment of iberdomide combinations in the frontline setting.” Iberdomide is currently being studied (versus lenalidomide) as maintenance therapy following autologous stem cell transplant (ASCT) in a phase 3 trial.

Mezigdomide in RRMM

Mezigdomide was combined with either bortezomib and dexamethasone (MeziVd) or carfilzomib and dexamethasone (MeziKd) in RRMM patients who had received 2 to 4 prior regimens or MeziVd-1.0 mg in RRMM patients who had received 1 to 3 prior regimens in the phase 1/2 CC-92480-MM-002 trial. The most common grade 3/4 TEAEs were hematologic and included neutropenia and thrombocytopenia with MeziVd and neutropenia and infections with MeziKd or MeziVd-1.0 mg. Dose reductions of mezigdomide due to TEAEs were required in 25% to 40% of patients, depending on the dose and combination. The ORR was 75.0% with MeziVd (21/28); 84.2% with MeziVd-1.0 mg (32/38); and 85.2% with MeziKd (23/27). Median time to response (range) was 1.38 (0.7-3.3), 0.89 (0.7-2.4), and 0.95 (0.9-5.1) months in the MeziVd, MeziVd-1.0 mg, and MeziKd cohorts, respectively. Median duration of response was 10.4 and 11.9 months in the MeziVd and MeziKd cohorts and was not reached in the MeziVd-1.0 mg group. These data support further exploration of mezigdomide in phase 3 studies. Mezigdomide is currently being studied in the SUCCESSOR-1 and -2 phase 3 trials.


Venetoclax, a potent oral BCL-2 inhibitor, has the potential to be the first biomarker-directed therapy for patients with RRMM positive for the t(11;14) translocation, who tend to exhibit higher BCL-2 levels.

Venetoclax Combinations in t(11;14)-Positive RRMM

In an ongoing phase 2 study, venetoclax, carfilzomib, and dexamethasone (VenKd) was used to treat patients with t(11;14)-positive RRMM. Patients were randomized 5:3:5 to receive K (70 mg/m2 weekly) and d (40 mg) in combination with daily venetoclax (400 mg or 800 mg) or Kd alone. The current analysis included 56 patients. The most common TEAEs, occurring in at least half of patients, were diarrhea, nausea, fatigue, and vomiting and were more common in venetoclax-treated patients than in those treated with Kd alone. Grade ≥3 TEAEs occurring in at least 20% in any group were lymphopenia, neutropenia, and hypertension. Grade ≥3 infection rates were higher in the VenKd groups vs Kd alone (29% vs 20% vs 11%). After a median follow-up of approximately 1–2 years, ORRs (95% CI) were 94% (71-100), 95% (75-100), and 58% (34-80) in the venetoclax 400 mg, 800 mg, and Kd-alone groups, respectively. CR/sCR rates were 29, 50, and 11%, respectively. Median time to response was 1.0, 1.0, and 2.4 months, and 12-month progression-free survival (PFS) estimates were 67, 85, and 79%, with median PFS of 42.4 months. Overall survival (OS) data are not yet mature. Study enrollment is ongoing. According to the researchers, treatment with VenKd was well tolerated and produced favorable responses in at least 90% of patients.

The CANOVA study compared once-daily oral venetoclax and dexamethasone (Vd) versus pomalidomide and dexamethasone (Pd) in 263 patients 18 years and older who had t(11;14)-positive RRMM and had received ≥2 prior lines of therapy. Vd did not significantly improve PFS relative to Pd, the primary end point of the trial. Patients receiving Vd showed a median PFS of 9.9 months compared with 5.8 months with Pd (HR = 0.823, 95% CI: [0.596, 1.136]; P=0.237). The safety profile of Vd was generally consistent with the known safety profiles when used as single agents, and no new safety signals emerged. The most common AEs in the Vd group were infection (61%), diarrhea (41%), lymphopenia (24%), and nausea (22%). The most common AEs in the Pd group were neutropenia (63%), infection (57%), thrombocytopenia (39%) and anemia (35%).

Bispecific Antibodies and CAR T-Cell Therapies

Strategies for Managing Infection Risk With Teclistamab

Bispecific antibodies (bsAbs) that target B-cell maturation antigen (BCMA) may contribute to increased infection risk in RRMM patients and warrant preventive measures against infection.

To devise recommendations for clinical practice, researchers analyzed data from the phase 1/2 MajesTEC‑1 study of teclistamab, a BCMA×CD3 bsAb, involving 165 RRMM patients. After a median follow-up of 21.7 months, approximately 78% of patients (n=129) developed infections, with over half of the overall study participants developing grade 3/4 infections. Twenty patients (12.1%) died due to infections (17 had COVID-19). Median time to first onset of any grade infection was 1.7 months. Overall, 70.9% of patients had at least 1 IgG value <400 mg/dL and 45.5% received intravenous immunoglobulin (IVIG). Grade 3/4 neutropenia occurred in 65.5% of patients at a median of 2.3 months, and 53.3% of patients received granulocyte colony-stimulating factor (G-CSF).


BsAbs and High-Risk/Extramedullary Disease

At IMS, the findings of a systematic review of 9 studies evaluating whether bsAbs are effective in managing extramedullary disease (EMD) and high-risk cytogenetic abnormalities (HRCAs) in RRMM—including ORRs of the entire cohort (N=660)—were reported. The ORRs for EMD and HRCAs were reported in 3 (n=78) and 4 (n=100) studies, respectively. From the studies that reported ORR for EMD, talquetamab (GPRC5D×CD3) was shown to have the highest ORR (0.45 [0.17; 0.77]), followed by elranatamab (BCMA×CD3; 0.38 [0.23; 0.55]) and teclistamab (0.36 [0.19; 0.56]). There was no significant difference in ORR among the agents with respect to EMD status. In studies that reported ORR for HRCAs, talquetamab had an ORR of 0.67 (0.17; 0.77) followed by teclistamab (0.61 [0.43; 0.76]), and elranatamab 0.55 (0.36; 0.73). Similarly, there was no significant difference in the ORR among these agents with respect to HRCA status. According to the researchers, EMD responses are significantly lower than the full cohort ORR; however, it is encouraging that responses to high-risk MM closely approximate ORR of these agents. The authors note that the reporting of EMD responses “needs to be improved, and clinical trials should report EMD responses distinctly, as it directly informs clinical decisions.”

Teclistamab Treatment in Real-World Settings

Teclistamab, a bsAb recently approved for RRMM patients who have undergone ≥4 lines of therapy, has shown promise in clinical settings. Researchers from the Dana-Farber Cancer Institute/Brigham and Women’s Hospital reported their experience with teclistamab in 34 patients (median age 65; median 6 prior lines of therapy). Notably, 62% of patients had HRCAs, and 38% had EMD. Observed hematologic toxicities included anemia, neutropenia, and thrombocytopenia, and cytokine release syndrome (CRS), primarily grade 1 or 2, occurred in 56% of patients. Neurological toxicity was minimal, affecting 3% of patients. Infectious complications were noted in 32% of cases, with 9% classified as grade 3 or higher and no treatment-related deaths recorded. At a median follow-up of 6 weeks, ORR was 44%, with 9% achieving CR and 29% reaching VGPR or better. Teclistamab also demonstrated efficacy in patients with renal dysfunction, EMD, and/or HRCAs. According to the researchers, “teclistamab treatment in a commercial setting generated comparable responses to the previously reported clinical trials without any new toxicity signals.”

Forimtamig in RRMM

Forimtamig, a GPRC5D×CD3 T cell–engaging bsAb, has demonstrated significant clinical efficacy across various high-risk subgroups of RRMM patients, according to findings from a phase 1a dose-escalation study. In this first-in-human study, which included patients who were heavily pretreated and refractory to both proteasome inhibitors and immunomodulatory drugs, forimtamig exhibited an ORR of 66.7%, with 54.2% of patients achieving a VGPR or better. Importantly, the median duration of response was 12.2 months, with a majority of responders maintaining their responses at the time of data cutoff. Researchers also saw promising results in specific high-risk subgroups, including patients aged ≥65, those with >4 prior lines of therapy, and individuals with HRCAs. Of note, patients with 1q21 gain, known to be a HRCA, exhibited an ORR of 86.7%. Forimtamig also demonstrated effectiveness in patients previously treated with BCMA-targeted therapies, including antibody-drug conjugates, bsAbs, and CAR T-cell therapy, suggesting its potential as a salvage therapy. The study’s authors emphasized the need for further optimization of forimtamig dosing and scheduling and ongoing evaluation of its long-term treatment benefits, particularly in patients with high-risk disease characteristics.

CARTITUDE-4 Updated Results

The CARTITUDE-4 trial is a global, open-label, randomized controlled trial comparing ciltacabtagene autoleucel (cilta-cel) with physician’s choice of standard of care (SOC): either pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd) in lenalidomide-refractory MM patients. As of November 1, 2022, median follow-up was 15.9 months (range, 0.1–27), and 208 patients were randomized to cilta-cel (of whom 176 received cilta-cel) and 211 to SOC. Cilta-cel significantly improved PFS compared to SOC (median not reached vs 11.8 months), with a hazard ratio (HR) of 0.26 (P< 0.0001). In prespecified subgroup analyses, cilta-cel consistently demonstrated improved PFS across various patient subgroups. This includes patients <65 and 65–75 years of age and those who have any of the following: HRCAs, ≥1 HRCAs, ISS stage III, soft tissue plasmacytomas, high bone marrow plasma cell counts, or triple-class–refractory disease. Cilta-cel also showed efficacy when compared to both PVd and DPd. According to the researchers, the benefit shown was “similar to that seen in the overall ITT population, confirming efficacy of a single cilta-cel infusion in a range of clinically relevant MM subgroups.”

Anti-GPRC5D After Anti-BCMA CAR T-Cell Therapy

Autologous GPRC5D CAR T-cell therapy shows promising results in RRMM patients who have previously undergone anti-BCMA CAR T-cell therapy, according to the latest findings from a phase 2 trial. In this single-arm study conducted in China, 11 patients with RRMM who had previously received anti-BCMA CAR T-cell therapy were enrolled and treated. At a median follow-up of 14.8 months, all 11 patients achieved a response, with 45% achieving a CR or better. Of note, 73% of patients were MRD negative in bone marrow. The median PFS was 6.4 months, and 45% of patients remained progression-free at the time of analysis. The safety profile of GPRC5D-targeted–CAR T-cell therapy was manageable, with grade 3 or higher hematological toxicities being the most common AEs. CRS occurred in 91% of patients, but all cases were grade 1 or 2, and CRS was effectively managed with tocilizumab and dexamethasone. No neurological toxic effects were reported. According to the researchers, “GPRC5D-targeted CAR T-cell therapy is clinically active with a favorable safety profile in patients who do not respond to or relapse after anti-BCMA CAR T-cell therapy.”

Advances in Rapid CAR T-Cell Platforms

PHE885, a fully human CAR T-cell agent manufactured using the T-Charge platform, has demonstrated durably persistent CAR T expansion in a phase 1 study conducted at the Dana-Farber Cancer Institute. Though CAR T-cell therapy targeting BCMA has shown benefit in the RRMM setting, challenges such as lengthy manufacturing times and limited in vivo persistence still need to be resolved. PHE885 had previously demonstrated a 98% ORR across all dose levels, with a 100% ORR at doses exceeding 5×106 CAR T cells. The latest analysis of serial samples from 32 patients suggested that the manufacturing process successfully preserved stem-like memory T cells in the final product, resulting in a diverse and proliferative CAR T expansion following infusion. CAR T cells also maintained a diverse T-cell receptor repertoire, particularly in patients with long-term persistence. The researchers concluded that “T-Charge… successfully preserved stem-like memory T cell clones in the final product, leading to a highly heterogeneous and proliferative CAR T expansion with durable persistence.”

A fourth-generation BCMA CAR T-cell therapy, InstanCART, has exhibited promising results in the treatment of RRMM during a phase 1 clinical trial. Typically, CAR T-cell therapy has prolonged production times and high costs. The traditional production process, which the China-based researchers have called TraditionCART, takes 9–14 days, leading to extended vein-to-vein times and disease progression during production. By contrast, InstanCART, manufactured using the Instant Manufacturing Platform, offers a streamlined production process, optimizing T cell function. The latest phase 1 clinical trial compared the safety and efficacy of TraditionCART and InstanCART in RRMM patients. Both approaches demonstrated favorable safety profiles, with no grade 3 or greater neurotoxicity or CRS observed. However, InstanCART showed lower rates of grade 3 AEs than did TraditionCART. Notably, InstanCART achieved an ORR of 100%. There was no statistically significant difference in PFS and OS between InstanCART and TraditionCART. However, the expansion and duration of InstanCART cells was significantly higher than TraditionCART cells, highlighting its potential for enhanced therapeutic benefit. According to the researchers, InstanCART was well tolerated and showed noninferior efficacy and more encouraging pharmacokinetic profile than TraditionCART for RRMM therapy. The study is ongoing, and long-term follow-up will assess durable efficacies.


Jointly provided by the MMRF and RedMedEd.

This educational activity is supported by educational grants from AbbVie Inc., Bristol Myers Squibb, and GSK, and sponsorship from Legend Biotech USA Inc.

Non-BCMA targeting bispecific antibodies are a relatively new class of therapeutics. In our Patient Webinar on October 11, 2023, Drs. Ajai Chari (UCSF) and Suzanne Trudel (University of Toronto, Princess Margaret Hospital, Ontario, Canada) provided fascinating updates on this emerging class of agents.

Bispecific antibodies belong to the drug class known as T-cell engagers, which also includes CAR T-cells. Unlike CAR T-cells, which are engineered (over the course of 4-6 weeks) from a patient’s own T-cells to better recognize and kill myeloma cells, bispecific antibodies are an “off-the-shelf” treatment that can bind to both myeloma cells and to T cells at the same time, bringing them in close proximity so that the T cells can recognize and kill the myeloma cells. There are now three bispecific antibody therapies approved in the US for myeloma patients who have received at least four previous lines of therapy; two of these bind to BCMA on the surface of myeloma cells, and one binds to a molecule called GPRC5D on the surface of myeloma cells.

Dr. Chari began by discussing Talvey (talquetamab), a GPRC5D-targeting bispecific antibody approved for use in the US. Historically speaking, the bispecific antibody drug class offers increased activity in highly pre-treated myeloma patients (those who have already received 4 or more lines of therapy). The relative activity of a number of different drugs in this patient population is seen in this slide:

In comparison to current standards of care, such as Pomalyst/dexamethasone, it is clear from this figure that the three currently approved bispecifics—teclistamab (Tecvayli), talquetamab (Talvey), and elranatamab (Elrexfio)—have superior activity in this patient population in terms of both progression-free survival and duration of response (NR means the duration of response was not reached, as so many patients were still responding at the time the data was collected). Dr. Chari also mentioned that of the 288 patients enrolled in the Talvey Phase1/2 trials, 51 had received prior therapy with T-cell engagers, and their response rate compared to those who had not previously received such therapy was only slightly lower (65% vs 73%).

Regarding side effects and adverse occurrences, Dr. Chari provided some further fascinating facts on Talvey not demonstrated on a slide. Dr. Chari stated that patients who experienced more severe side effects (particularly skin rashes and nail issues) also responded better to Talvey. As a result, there is a correlation between side effects and pharmacological action, which may give patients who are experiencing discomfort from side effects optimism that the medication may work for them. He added that patients with the most severe adverse effects can benefit from other treatments or dose decrease, and that generally, these side effects do get better with time.

Next, Dr. Trudel discussed cevostamab, a FcRH5-targeting bispecific antibody that is still in clinical trials. Two noteworthy pieces of information emerged from her presentation:

Thank you to these two amazing doctors, and also to our patient speaker, Nick Lenoir, for sharing their knowledge! Nick was especially interesting, as he is currently receiving treatment with Talvey and is having issues with side effects, so he was very happy to hear that this meant he is more apt to respond to this therapy.

For more information on bispecific antibodies and other myeloma therapies, please visit our Treatment Options page

What is the threshold for achieving minimal residual disease (MRD) negativity after treatment?

MRD measurement aims to detect any myeloma cells that remain in the body after a complete response is achieved following treatment. MRD tests can detect at least 1 myeloma cell in 100,000 healthy bone marrow cells (a threshold of 1 × 10-5) and other tests can detect 1 cell in a million (a threshold of 1 × 10-6). As an example, when you collect 100,000 bone marrow cells and you don’t find any myeloma cells with testing, you are considered MRD negative (this is a threshold of 10-5) and similarly if you don’t find any myeloma cells within one million bone marrow cells (this is a threshold of 10-6). Currently, a threshold of 10-5 is used to define MRD negativity in clinical studies and the FDA drug development process. Deeper thresholds like 10-6 are being used and reported in clinical studies, but in practice it might be difficult to get the one million bone marrow cells needed to test at this threshold.

Sometimes patients may receive a result that is difficult to tell whether they are MRD positive or not. These results are considered below the level of detection and even though the result may not be zero, it is still a very good result. Regardless of your MRD status, it is always best to discuss your MRD test results and what they mean with your doctor.

Are MRD results being used to guide treatment decisions?

MRD testing is far from an experimental test. Testing has been well-validated based on extensive data from clinical studies. However, basing treatment decisions on MRD test results is not routinely done, especially outside of the academic medical center setting. For example, it is unclear whether patients who are MRD positive should get more treatment, whether patients who go from MRD negative to MRD positive should get treatment before development of clinical symptoms, and whether patients who are MRD negative no longer need maintenance therapy. Several clinical studies are ongoing to determine how MRD results might be used to guide treatment in the future. However, MRD testing results do provide some level of information for the patient and the doctor about the trajectory of the disease. What this means is that MRD test results help to inform doctors if and how the number of myeloma cells has changed since a patient’s last MRD test (that is, did the number of cells go up, go down, or remain the same?). This information will help patients and their doctors understand how the amount of myeloma in a patient’s body may be changing over time. Be sure to ask your doctor to put your MRD test results, over time, into context for you and where you are in your myeloma journey.

Is MRD testing covered by insurance?

MRD measured by flow cytometry is usually covered by insurance because it is typically part of bone marrow biopsy testing. MRD measured by next-generation sequencing (that is, the ClonoSEQ assay developed by Adaptive Biotechnologies) is FDA-approved and is widely covered for patients on Medicare. Medicare covers clonoSEQ at 100% for multiple myeloma, and 90% of all patients pay $0 out of pocket.  Patients will only receive a bill for unmet deductibles or coinsurance after the test is covered by insurance.  Call the Adaptive Patient Support team at 1-855-236-9230 or visit for 5-minute enrollment and rapid verification.

How often should blood tests and PET scans be performed following a response to treatment?

Once patients have completed their induction therapy and a stem cell transplant (if they were eligible for one) and begin maintenance therapy, blood tests are usually performed once a month. After about a year of maintenance therapy, the frequency of testing goes down to once every three months. Patients who have high-risk myeloma (for example, those who have the chromosome 17 deletion or other high-risk features) will be checked more frequently.

PET scans are not performed routinely after a response to initial treatment. PET scans are performed only when there is a change in lab values (such as M protein values begin to rise). At this time a PET scan will be conducted to see if the rise in M protein represents a significant relapse (that is, new lytic lesions in the bones can be visualized). 

How common is a partial response versus a complete response to treatment?

One of the most exciting things about myeloma therapy in 2023 is that, more than ever before, patients are achieving a very good partial response or better (a reduction of M protein in the blood by 90% or more) with treatment! The reason for these incredible responses is due to the availability of a variety of drugs that can be combined into three- and four-drug regimens. Ultimately, the type of response a patient achieves will depend on which regimen is given, but the use of these regimens can lead to a very good partial response and complete response in approximately 70% to 80% of patients. Furthermore, with the use of minimal residual disease (MRD) testing (that is, a test that can determine the number of multiple myeloma cells or DNA sequences still present in bone marrow after treatment), patients are reaching a deeper level of response called MRD negativity (no multiple myeloma cells or DNA sequences can be detected in the bone marrow). Patients who are MRD negative following treatment have been shown to live longer than those who remain MRD positive.

How can myeloma patients reduce the pain and stress of a bone marrow biopsy?

Undergoing the procedure of a bone marrow biopsy is one of the most stressful tests myeloma patients have to endure during their journey. The reason it is stressful is that the procedure, unfortunately, is associated with pain and anxiety. Many institutions have the means to reduce pain and anxiety in their patients, so if you are concerned, you need to have an upfront discussion with your care team in order to meet your needs. Luckily, there are many ways, both with and without medication, to prevent pain and anxiety during a bone marrow biopsy. Some examples are listed below.

To find the right solution for you that your institution offers, please discuss your options for pain control with your care team.

The 2023 American Society of Clinical Oncology (ASCO) annual meeting was held from June 2 to 6 in Chicago! Clinicians and researchers gathered to present and discuss several updates in multiple myeloma relating to:

Let us break down the key findings for you…

CAR T-Cell Therapy

New data on both Carvykti and Abecma, which are FDA approved CAR T-cell therapies that target BCMA on myeloma cells, was reported.


Carvykti is approved for patients with multiple myeloma (MM) after at least four previous treatments. Given the success of CAR T-cell therapy in patients who have failed many different treatments and have relapsed/refractory MM (RRMM), there is an interest in testing CAR T-cell therapy for patients who have received fewer prior therapies.

In a late-breaking abstract presentation, Dr. Binod Dhakal and colleagues reported their findings from CARTITUDE-4, the first randomized phase 3 study evaluating the efficacy and safety of Carvykti in 419 patients with RRMM that no longer responded to treatment with Revlimid (ABSTRACT LBA106). Findings from CARTITUDE-4 were simultaneously published in the New England Journal of Medicine. The study compared Carvykti with standard of care treatments (Pomalyst, Velcade, and dexamethasone [PVd] or Darzalex, Pomalyst, and dexamethasone [DPd]) in Revlimid-refractory patients who received one to three prior lines of therapy, including a proteasome inhibitor and an IMiD. The results showed:

These findings demonstrate the dramatic benefit of Carvykti over the standard of care in 1 to 3 prior lines of therapy and highlight the potential for Carvykti to be a promising new treatment option for patients in this setting.

In a separate presentation, Dr. Yi Lin and colleagues from the Mayo Clinic reported final results from CARTITUDE-1, which was a phase 1/2 study of Carvykti in heavily pretreated patients with RRMM—in individuals who received 3 prior lines of therapy or were double refractory to a proteasome inhibitor (PI) such as Velcade, Kyprolis or NInlaro and immunomodulatory drug (IMiD) such as Revlimid or Pomalyst; and had received prior PI, IMiD, and anti-CD38 antibody therapy (ie, Darzalex or Sarclisa). (ABSTRACT 8009).  A previous publication by Dr. Thomas Martin and researchers from the University of California, San Francisco reported an overall response rate (ORR) of 98%. These updated results, including analyses of high-risk patient subgroups, showed heavily pretreated patients with RRMM were able to live an average of 35 months before their myeloma progressed.

A longer median progression free survival (PFS)that is, the length of time during and after treatment in which a patient is living with a disease that does not get worsewas observed after a single infusion of Carvykti than any previously reported therapy in heavily pretreated patients with RRMM. Patients continue to be followed for safety and survival in the CARTITUDE long-term study.


A pair of presentations highlighting recent findings on Abecma, the first CAR T-cell therapy approved for RRMM, were presented. Researchers presented patient-reported outcomes on health-related quality of life from the phase 3 KarMMa-3 trial (ABSTRACT 8032). Health-related quality of life captures information on the physical and mental health status of individuals, and on the impact of disease and treatment on a patient’s quality of life. The results from the patient-reported outcomes showed statistically significant and clinically meaningful improvements in health-related quality of life including cognitive functioning, fatigue, and pain reduction for patients with RRMM who received Abecma compared with standard treatment regimens.

B-cell maturation antigen (BCMA) CAR T PHE885

Adam Sperling and colleagues from Dana-Farber Cancer Institute reported updated results from a phase 1 study of BCMA-targeting CAR T PHE885 (ABSTRACT 8004), which uses a new development process that shortens the manufacturing time from several weeks to less than two days. The results showed an ORR of 100% in patients who received the highest dosage of PHE885 and 98% in all 49 patients.  CRS was observed in 96% of patients, which is a similar rate seen in patients receiving CAR T-cell therapy. Only 28% of patients required bridging chemotherapy. A phase 2 study is underway in patients with RRMM, and evaluation in earlier lines of therapy is about to begin.

Bispecific Antibodies (also known as T-cell engagers)


Tecvayli was the first approved off-the-shelf BCMA-directed bispecific antibody for the treatment of patients with RRMM. The approval was based on data from the pivotal phase 1/2 MajesTEC-1 study, which showed an ORR of 63% in patients who received Tecvayli. In this presentation, Dr Niels van de Donk and colleagues from the Netherlands presented updated findings. Patients had a median of 5 prior treatments  (92% Darzalex exposed; 78% triple-class refractory; 81% Darzalex-refractory).The results showed:

These long-term follow-up data support Tecvayli as a safe and effective off-the-shelf BCMA bispecific therapy for patients with RRMM.

Tecvayli + Talquetamab

Dr. Yael Cohen and researchers from Israel reported initial results from the phase 1 RedirecTT-1 trial that examined the combination of Tecvayli with talquetamab, an investigational bispecific antibody targeting GPRC5D, an immunotherapeutic target like BCMA on myeloma cells (ABSTRACT 8002). This trial is the first to test the combination of two bispecific antibodies with two different myeloma cell targets (that is, BCMA and GPRC5D) with the hope of overcoming resistance to single agent bispecific antibody therapy. The goals of this study were to evaluate safety and identify an optimal dosage of the combination of bispecific antibodies. The results showed:

Combining BCMA-targeted Tecvayli with GPRC5D-targeted talquetamab yielded high response rates in patients with RRMM and support the continued evaluation of this combination therapy.

Darzalex + Talquetamab

Dr. Bhagirathbhai Dholaria and colleagues from Vanderbilt University Medical Center reported findings from the phase 2 TRiMM-2 study in patients with heavily pretreated RRMM who received investigational talquetamab in combination with Darzalex (ABSTRACT 8003). The study included some patients who were previously exposed to anti-CD38 (88%) inhibitors like Darzalex or Sarclisa, BCMA-targeted therapy (54%), and CAR-T therapy (17%).  Patients in the TRiMM-2 study were treated with talquetamab at a dose of either 0.8 mg/kg every two weeks or 0.4 mg/kg weekly in addition to Darzalex. The ORR was 84% for patients who received the higher dose of talquetamab and 71% for those who were treated with the lower dose. Ongoing studies will continue to examine the clinical potential of this combination of therapy.

Talquetamab Monotherapy

Dr. Carolina Schinke from University of Arkansas for Medical Sciences presented updated findings from the phase 1/2 MonumenTAL-1 study of talquetamab in patients with RRMM (ABSTRACT 8036).  Patients were treated with talquetamab at the recommended phase 2 dose (RP2D) of 0.8 mg/kg biweekly or 0.4 mg/kg weekly with step-up doses. The results showed:


Elranatamab is an investigational off-the-shelf BCMA-directed bispecific antibody in the same class as Tecvayli, being evaluated as monotherapy in patients with RRMM.  In this presentation, Dr. Mohamad Mohty and colleagues from France reported findings from the MagnetisMM-3 study that showed 61% patients who have not been exposed to a prior BCMA-directed therapy achieved a response to elranatamab monotherapy (ABSTRACT 8039). The most common side effects were CRS (66%) and low red blood cell counts (59%).

In a separate presentation, Dr. Ajay Nooka and colleagues from Emory University reported their findings from a pooled analysis of patients treated with prior BCMA-directed therapies enrolled in the MagnetisMM program (ABSTRACT 8008). The results showed:

These results support elranatamab monotherapy as a treatment option for patients with RRMM who have been pre-treated with another BCMA-targeting agent.


Linvoseltamab is another investigational BCMA-targeting bispecific antibody for patients with RRMM who previously received 3 or more prior treatments. Dr Hans Lee and researchers presented findings from the phase 2 LINKER-MM1 trial that tested 50 mg and 200mg dosages of linvoseltamab (ABSTRACT 8006). The results showed an overall response rate of 71% for patients who received the 200 mg dose and 50% for those who were treated with 50 mg of linvoseltamab. Cytokine release syndrome was the most common side effect observed in patients receiving either dosage. A phase 3 trial, LINKER-MM3, will be initiated in patients with RRMM.

New Treatment for Newly Diagnosed Multiple Myeloma


In patients with newly diagnosed multiple myeloma (NDMM), triplet or quadruplet induction regimens, high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) remain a standard of care. Empliciti is approved in combination with other medications such as Revlimid or Pomalyst and dexamethasone for patients with RRMM, but its role in NDMM has not been studied. In this clinical trial (ABSTRACT 8000), Dr. Stefan Krop and researchers from Germany compared Empliciti plus Kyprolis, Revlimid, and dexamethasone (KRd) to KRd in transplant-eligible NDMM patients up to 70 years. The results showed the addition of Empliciti to KRd significantly improved the rate of early, deep minimal residual disease (MRD)-negative remission (50% Empliciti-KRd vs 35% KRd) in transplant-eligible NDMM. Future studies will explore the potential role of Empliciti in NDMM.

Maintenance Therapy

Kyprolis, Pomalyst, dexamethasone (KPd)

While maintenance or continuous therapy with Revlimid is the current standard of care for patients with standard-risk myeloma following induction therapy and ASCT, current data suggest those with high-risk myeloma should receive a proteasome inhibitor such as Velcade, either as a single agent or combined with Revlimid, or even a triplet like Velcade, Revlimid, and dexamethasone (VRd).

Dr. Ajay Nooka and colleagues from Emory reported their findings of a phase 2 trial that assessed KPd as maintenance therapy patients with high-risk myeloma (ABSTRACT 8001).  More than half of patients (59%) enrolled in the single arm trial were Black. High-risk myeloma was defined by the presence of certain changes in a patient’s DNA such as translocation of (4;14) or (14;16), deletion of 17p, gain of 1q, or greater than 20% circulating tumor cells.  Double-hit myeloma (as defined by the presence of 2 or more high-risk genetic mutations was seen in 59% of patients in this study. The results showed:

In patients with high-risk myeloma, KPd maintenance deepened responses and may be able to fill an unmet treatment need in this patient population. Be sure to hear what myeloma experts have to say about the meeting’s presentations here.

When is a clinical study the best option for a patient with high-risk smoldering multiple myeloma (SMM)?

A clinical study is the only option to gain access to treatment of high-risk SMM at this time. If you have a multiple myeloma precursor condition (monoclonal gammopathy of undetermined significance [MGUS] or SMM), the standard of care is watchful waiting—that is, monitoring you closely to determine if you progress to myeloma and treating you only when progression occurs. The reason patients with MGUS or SMM are not treated is that neither condition is associated with organ damage or any of the symptoms commonly associated with myeloma. Furthermore, no more than half of SMM patients progress to myeloma within the first 5 years after diagnosis, and the number is even smaller for patients with MGUS. Additionally, administering treatments (typically the same drugs used to treat myeloma) to patients who have precursor conditions that may or may not advance to multiple myeloma could lead to unwanted side effects while also yielding no benefit.

High-risk SMM may warrant treatment rather than watchful waiting and may yield the benefits of delaying the onset of active myeloma and increasing life expectancy. Treatment, if recommended at this stage, should take place only in the context of a clinical study.

It is also important to note that not every clinical study focuses on therapeutic intervention for precursor conditions. There are several observational studies and research studies for patients with MGUS or SMM that involves the collection of bone marrow and blood samples to help clinicians better characterize the conditions and to better predict which patients are at the highest risk of progression to myeloma. Additionally, non-pharmacologic interventional studies, such as diet and lifestyle modification, are also available to determine whether these types of interventions modify the diseases at all.

Search for a clinical trial in your area access the MMRF’s Clinical Trial Finder
( or let an MMRF patient navigator help guide you through the process (1-888-841-6673 or [email protected]).

How can I join a clinical study if my doctor has not brought up the possibility of joining one?

As with any aspect of clinical care for a patient with multiple myeloma or one of its precursor conditions, open communication with the care team is important. You (and your caregivers) should always feel comfortable asking your doctors about alternative options for your care including whether or not a clinical study should be considered. All clinicians expect these questions and they want their patients to be happy with their care. You should not worry about your clinician’s feelings if you wish to seek care with a different doctor or to enroll on a clinical study.

Is there a negative impact on a patient’s relationship with their care team if he or she eventually withdraws from a clinical study due to life events or some other reason?

A withdrawal from a clinical study is never held against a patient! Of course, most clinicians would like patients to stay on a clinical study for the integrity of the data, but patients always have the right to discontinue participation for any reason. Patients will still receive quality care and respectful treatment and will in no way be punished for deciding not to participate. Clinicians understand that circumstances can change in a patient’s life that may make it difficult to continue participating.

What determines if patients with monoclonal gammopathy of undetermined significance (MGUS) will eventually advance to active multiple myeloma or something else like Waldenström’s macroglobulinemia and can anything be done to try and prevent this progression?

MGUS almost always occurs before a person develops myeloma or another malignant plasma cell disease (such as Waldenström’s macroglobulinemia or lymphoma). MGUS is associated with a risk of progression of approximately 1% per year. Therefore, the longer you have MGUS the higher the risk is that you will progress. For example, if a patient has had MGUS for 10 years there is a 10% risk and for 30 years the risk is 30%. Overall, the risk of progression is continuous and unfortunately, there are no data to definitively identify patients who have had MGUS for 10 to 15 years or longer that will never develop myeloma. The reason for this is that an MGUS cell clone might be stable during this time, but the longer one has this clone the more likely the clone will evolve to myeloma or another malignant plasma cell disease.

Immune regulation is thought to prevent the switch from MGUS to myeloma. Some data suggest that a patient’s immune system keeps the potentially malignant clone in check. For instance, MGUS that is diffuse (that is, spread out) in the bone marrow has a much lower risk of progression than clustered MGUS. Clustering excludes a patient’s immune cells from controlling the clone. Clusters of MGUS cells make it harder for the immune cells to get to the cells in the center of the cluster allowing the clone then to evolve and change and that is what we get into trouble with.

For now, doctors are unable to predict which MGUS patients will progress and as a result patients should be monitored continuously.

What does the hazard ratio mean when clinical trial data are reported?

The hazard ratio (HR) is a value calculated by statistical analysis that estimates survival endpoints such as overall survival or progression-free survival between two treatment groups over the entire duration of a randomized clinical trial (that is, a study that compares two different treatment groups: the experimental treatment versus the control treatment). The HR value (usually a number greater than or less than 1) indicates how much one treatment is better or worse than the other. For example, if the experimental treatment is better than the control treatment then the HR is less than 1 and if it is worse than the control treatment then the HR is greater than 1. A HR that is equal to 1 means equal efficacy between the two treatment groups.

What new data from myeloma precursor conditions should patients be aware of?

Several interventional trials are under way using newer immunotherapies in smoldering multiple myeloma patients who have the highest risk of developing myeloma within 1 to 2 years. The objective is to determine if immunotherapy has curative potential in these patients. Using immunotherapies earlier in the disease may be more beneficial than using them at relapse since a patient’s immune system is healthier at that stage. However, it is important to note that immunotherapy approaches come with a risk of infections. Infection risk for smoldering multiple myeloma patients may be quite significant considering they are asymptomatic to begin with. Also, it is not yet known whether targeting B-cell maturation antigen (BCMA) with a CAR T cell or bispecific antibody may wipe out the regulatory immune microenvironment that is necessary to control the malignant clone.