End of Year Wrap Up: Key Updates in Myeloma in 2021 and Possible Upcoming FDA Updates

The year 2021 yielded promising clinical research in the myeloma space, such as the extended findings of the phase 2 GRIFFIN trial (NCT02874742) of combination therapy with daratumumab (Darzalex) in patients with transplant-eligible myeloma as well as results that will support the FDA’s upcoming decision on the approval of ciltacabtagene autoleucel (cilta-cel) in February 2022. According to Yael, there is much to look forward to in the new year.

Presented during the 2021 American Society of Hematology Annual Meeting and Exposition, the extended 2-year findings of the GRIFFIN trial—which assessed the use of daratumumab, lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (D-RVd) plus autologous stem cell transplant (ASCT) followed by daratumumab plus lenalidomide maintenance in newly diagnosed myeloma—revealed that D-RVd provided robust, durable responses in patients with transplant-eligible newly diagnosed multiple myeloma.¹ Findings from the trial indicated that after a follow-up of 38.6 months, patients treated with the investigational regimen experienced a stringent complete response (CR) rate of 66.0% compared with 47.4% among patients treated with RVd alone (P = .0096). Moreover, MRD negativity rates in both populations were 64% and 30%, respectively. Additionally, despite not being powered to assess progression-free survival (PFS), investigators reported a 36-month rate PFS of 88.9% in the quadruplet arm compared with 81.2% in the triplet arm.

“The addition of daratumumab…really produced an upgrade [in terms] of the MRD negativity in the first line,” Cohen, senior physician in the Department of Hematology at Tel-Aviv Sourasky Medical center, stated in an interview with CancerNetwork®.

Moreover, she expressed excitement for the potential approval of cilta-cel for patients with relapsed/refractory disease in the coming year. The CAR T-cell product was recently assessed as part of the multicohort phase 2 CARTITUDE-2 study (NCT04133636), which enrolled patients with previously treated, progressive disease.² Findings from the trial indicated that patients achieved an overall response rate of 95% (95% CI, 75.1%-99.9%), including a rate of CR or better of 85% (95% CI, 62.1%-96.8%) and a rate of very good partial response or better of 90% (95% CI, 68.3%-98.8%). The median duration of response was not reached. Investigators also reported that patients achieved a 6-month PFS rate of 95% (95% CI, 69.5%-99.3%) and a 12-month PFS rate of 84% (95% CI, 64.0%-94.7%). A total of 13 patients were evaluable for minimal residual disease (MRD) at the 10-5 threshold, 92% of whom were reported to be MRD negative.

In an interview, Cohen highlighted her excitement for upcoming findings, her experiences working as a hematologist in Israel, and the need to make CAR T-cell products more widely available for patients with multiple myeloma.

The FDA is set to make a decision regarding cilta-cel for the treatment of patients with relapsed/refractory multiple myeloma in 2022. What do you feel would be the implications of an approval?

It would be a really great thing. Hopefully, it will be accessible. Idecabtagene vicleucel [Abecma], a BCMA-directed] CAR T-cell therapy, has been approved in March 2021, but they are facing some access problems and logistical problems.³ [Therefore], it remains to be seen what will happen with cilta-cel. Hopefully, it might be another option and maybe it will go better. It’s really a game changer and it’s very exciting. I am a hematologist from Israel and I know we are not getting it immediately upon approval; it will start here in the United States. [However], we are very hopeful that it will also be available in our country for our patients.

Are there any other upcoming regulatory decisions coming up in 2022 in the myeloma space that you’re looking forward?

[In terms of] regulatory decisions, I know some of the bispecific T-cell engager [BiTEs] products are in accelerated approval and some are [due] to enter accelerate approval. I’m not sure exactly how they’re spaced out in the upcoming year, but surely they will be coming up soon. We are certainly waiting. Those are the big things.

Were there any clinical trials that read out in 2021 that you felt were practice changing?

The GRIFFIN trial, which is a trial for [patients with] newly diagnosed myeloma [who] were transplant eligible. This is the addition of daratumumab to first-line therapy. There was a standard practice of VRd [plus] transplant, VRd consolidation, and then lenalidomide and (dexamethasone); this is the [regimen from the] IFM 2009 trial [NCT01191060]. This was also way that we treat patients in our country—in Israel. In the United States, I believe it’s the standard.

The estimates for first-line therapy will yield maybe 7 or 8 years of progression-free survival. That’s a huge change because where we were at 4 to 5 years [previously]. Hopefully, if we start the patients off like this, then by the time they progress, we will maybe be able to offer them a much better treatment, maybe even curative treatment. I’m sure all these CAR T-cell [products] and BiTEs will be mature and we will have them available. This is a major leap forward for myeloma.

References

1. Laubach JP, Kaufman JL, Sborov DW, et al. Daratumumab (DARA) plus lenalidomide, bortezomib, and dexamethasone (RVd) in patients (pts) with transplant-eligible newly diagnosed multiple myeloma (ndmm): updated analysis of GRIFFIN after 24 months of maintenance. Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 79.
2. Cohen YC, Cohen AD, Delforge M, et al. Efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)–directed chimeric ntigen Receptor (CAR) T-Cell therapy, in lenalidomide-refractory patients with progressive multiple myeloma after 1–3 prior lines of therapy: updated results from CARTITUDE-2. Presented at 2021 American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 3866.
3. FDA approves idecabtagene vicleucel for multiple myeloma. News release. FDA. March 26, 2021. Accessed December 20, 2021. https://bit.ly/30KnliB