Welcome to our final day of coverage from the latest advances presented at the 20th International Myeloma Society (IMS) Annual Meeting. Highlights from today include recent findings on standard and emerging treatments including bispecific antibodies, and CAR T-cell therapy in patients with relapsed/refractory multiple myeloma (RRMM). Here’s a quick recap!
Sarclisa (isatuximab) is an anti-CD38 monoclonal antibody approved in combination with Kyprolis (carfilzomib) and dexamethasone (Isa-Kd) for patients with relapsed/refractory multiple myeloma (RRMM) after one or more prior therapy. The IKEMA trial, which compared the combination of Sarclisa, Kyprolis, dexamethasone (Isa-Kd) with Kyprolis and dexamethasone, showed that patients with RRMM (who had received 1-3 prior lines of therapy) benefit from the use of Isa-Kd, with a longer time before their disease returns (progression-free survival [PFS]) of 36 months compared to 19 months with Kd. In this final analysis of the IKEMA trial, French researchers reported a meaningful benefit in overall survival with Isa-Kd compared to Kd. Side effects associated with Isa-Kd, such as infusion reactions, diarrhea, and high blood pressure, were consistent with previous analyses, supporting it as a standard-of-care therapy for RRMM.
Yesterday we learned about the activity of venetoclax when combined with Kyprolis and dexamethasone in patients with a translocation of chromosomes 11 and 14 (t[11;14]). Today, researchers from Spain shared their findings from the Phase 3 CANOVA study that evaluated venetoclax and dexamethasone (VenDex) against pomalidomide and dexamethasone (PomDex) in patients with t(11;14)-positive RRMM who have received two or more prior treatments.
Their findings revealed that patients receiving VenDex showed a small improvement in progression free survival (the time before their disease came back) compared to PomDex (10 months vs 6 months) as well as an 8-month improvement in overall survival (32 months for VenDex compared to 24 months with PomDex. The most common side effects experienced by patients treated with VenDex included any infection, diarrhea, low white blood cell counts, and nausea (22%).
Forimtamig, a GPRC5DxCD3 T-cell-engaging bispecific antibody (BsAb), is currently being evaluated in patients with RRMM who have received one or more prior line(s) of therapy, and were refractory to a proteasome inhibitor (such as Velcade, Kyprolis or Ninlaro) and an immunomodulatory drug (such as Revlimid or Pomalyst). Forimtamig is in the same class as Talvey (talquetamab), which received FDA approval several weeks ago. Findings from an early phase study showed forimtamig induced deep and durable responses in heavily pre-treated pts and had a safety profile consistent with other investigational GPRC5D-directed therapies. (Carlo-Stella et al. ASH 2022).
In this abstract, researchers from the United Kingdom presented their analysis of clinical responses in high-risk patients. For this study, high-risk patients were defined as: age ≥65 years, >4 prior LOT, triple-class and penta-drug refractory disease, prior BCMA-targeted therapy (such as CAR-T or a bispecific antibody like Tecvayli aka teclistimab), high-risk cytogenetics (del(17p), t(4;14), t(14;16)), 1q21 gain (irrespective of other high-risk aberrations), International Staging System Stage III at baseline, and presence of soft tissue plasmacytoma (bone-based and extramedullary).
ORR across all dose levels of forimtamig was 67% and high ORRs were observed across all risk groups. Future studies will seek to identify the best dose and schedule of forimtamig for patients with RRMM.
Tecvayli (Teclistamab) was the first “off-the shelf” BCMA-targeted bispecific antibody approved for patients with heavily pretreated RRMM (patients who have received 4 or more lines of therapy). In this abstract, Dr Shonali Midha and colleagues from the Dana-Farber Cancer Institute in Boston shared their preliminary experience with the real-world use of Tecvayli. Their findings revealed that treatment with Tecvayli in a real-world setting showed similar responses to the previously reported clinical trials without any new side effects. The authors conclude that additional real-world follow up on the use Tecvayli in the real-world is needed to confirm these findings.
Carvykti (ciltacabtagene autoleucel) is approved for RRMM patients after at least four previous treatments. Given the success of CAR T-cell therapy in patients with RRMM who have failed many different treatments there is an interest in testing CAR T-cell therapy for patients who have received fewer prior therapies. Findings from the CARTITUDE-4 trial showed Carvykti significantly improved PFS compared to the standard of care (that is physician’s choice of either Pomalyst, Velcade and dexamethasone or Darzalex, Pomalyst, and dexamethasone. In this abstract, researchers from France reported findings from a prespecified subgroup of patients, including those aged < 65 yrs, patients who received 1 prior line of therapy (that is first relapse), ISS stage III, triple-class refractory, etc.
The results showed that Carvykti improved progression free survival in all subgroups, including by age, in those with high-risk features, and after first relapse. The authors conclude that these findings offer further support for the use of Carvykti in earlier lines of therapy.
Please be sure to listen to hear what myeloma experts had to say as they recap each day’s clinical research and discuss what these findings mean for myeloma patients here.
We look forward to more clinical updates in the months ahead!