Saturday was the third and final day of the 19th International Myeloma Society (IMS) annual meeting in Los Angeles, California. Highlights included updates from clinical trials evaluating existing chimeric antigen receptor (CAR)T-cell therapies for relapsed or refractory myeloma and final clinical efficacy and safety results of a four-drug regimen in newly diagnosed patients.
Darzalex in Newly Diagnosed Multiple Myeloma
In the first presentation, Dr. Douglas Sborov from the University of Utah School of Medicine presented the final analysis of the phase 2 GRIFFIN study which compared Darzalex, Revlimid, Velacade, and dexamethasone (D-RVd) to RVd. The results showed that the addition of Darzalex to RVd led to a clinically meaningful progression-free survival (PFS) benefit (that is, longer time until disease progression) favoring the D-RVd arm. No new safety concerns occurred with longer follow-up. These data support use of D-RVd induction/consolidation and Darzalex-Revlimid maintenance as a new standard of care in transplant-eligible patients with newly diagnosed multiple myeloma.
CAR T-cell Therapy
Carvykti (ciltacabtagene autoleucel)
Carvykti is a CAR T-cell therapy that targets B-cell maturation antigen (BCMA) similar to Abecma and received FDA approval earlier this year. Trials of Carvykti in various patient populations are ongoing and at this meeting four abstracts offered updates from Carvykti clinical trials.
The first abstract presented by Dr. Adam Cohen from the University of Pennsylvania revealed updated results from the phase 2 trial called CARTITUDE-2, which again showed unprecedented high response rates among patients who received 1–3 prior lines of therapy and were Revlimid-refractory. The results from 20 eligible patients showed that:
- 95% of patients responded
- All minimal residual disease (MRD)-evaluable patients achieved MRD negativity
- Toxicities including cytokine release syndrome (which is a flu-like syndrome consisting of fever, chills, and low blood pressure, commonly seen in a majority of patients after administration of CAR-T therapy) and neurotoxicity (such as headache, confusion, cognitive disorder) were manageable
The second abstract from CARTITUDE-2 presented by Dr. Adam Cohen from the University of Pennsylvania evaluated treatment with Carvykti in 13 patients with prior exposure to a BCMA-targeting antibody-drug conjugate (Blenrep). The results showed that:
- 61.5% of patients responded
- 8.5% of MRD-evaluable patients achieved MRD negativity
- Time before disease progression was 9.5 months
- Toxicities including cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome ([ICANS], a common side effect of the nervous system observed after CAR T-cell treatment that can include confusion or delirium) were manageable
The authors conclude that these results may inform treatment plans, including sequencing and washout period between BCMA-targeting agents.
An analysis of seven patients who had progressive myeloma after treatment with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and a BCMA-targeting bispecific antibody and received Carvykti showed:
- 57.1% of patients responded
- 28.6% of patients achieved MRD negativity
- Time before disease progression was 5.3 months
- Toxicities including cytokine release syndrome and ICANS were manageable
Findings from this patient cohort will better inform management plans for heavily pretreated patients.
Dr. Mounzer Agha from the University of Pittsburgh Medical Center reported findings from the final abstract featuring data from the phase 2 CARTITUDE-2 trial that included patients who experienced an early relapse after initial therapy. These patients have functionally high-risk disease and an unmet medical need, as early relapse post autologous stem cell transplantation (ASCT) is a poor prognostic factor. The results from 19 eligible patients showed:
- All patients responded
- 93% of patients achieved MRD negativity
The researchers note that ongoing follow up of this trial of Carvykti may offer hope for a new treatment option for this high-risk patient population with early clinical relapse following initial therapy.
bb21217
bb21217 is a BCMA-directed CAR T-cell therapy which uses the same CAR molecule as Abecma, the first CAR T-cell therapy approved for the treatment of relapsed or refractory multiple myeloma. Dr. Noopur Raje from Massachusetts General Hospital reported findings from a phase 1 trial of bb21217 in patients who received 3 or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or are double refractory to both classes. Data collected from 72 patients who received bb21217 showed that:
- All patients responded
- Safety is consistent with previous reports. CRS (in 75% of patients) and neurotoxicity (in 15% of patients) were generally mild
Bispecific Antibodies
ABBV-383 is a BCMA × CD3 bispecific antibody that has demonstrated promising activity in relapsed/refractory multiple myeloma. Updated results from the ongoing first-in-human phase 1 study of ABBV-383 that included 123 patients who received 3 or more previous lines of therapy reported that:
- 57% experienced a treatment response
- Of the 11 MRD-evaluable patients, 73% were MRD-negative
- Toxicities including cytokine release syndrome, fatigue, low red blood cell counts, and nausea were well managed
Please be sure to listen to expert insights on these trials from Dr. Ivan Borrello and Dr. Peter Voorhees here.
We look forward to more clinical updates in the months ahead!
