Sham Mailankody, MBBS
Although not yet approved for patients with relapsed/refractory multiple myeloma, chimeric antigen receptor (CAR) T-cell therapies have shown great promise, in addition to the various immunotherapy treatment options already available, according to Sham Mailankody, MBBS. Immunotherapy with checkpoint inhibitors, however, has encountered a rockier road in multiple myeloma.
During a presentation at the 2nd Annual Live Medical Crossfire: Hematologic Malignancies meeting presented in New York, NY, Mailankody, a medical oncologist/hematologist at Memorial Sloan Kettering Cancer Center, discussed current treatment options and shifting preferences, especially toward triplet combinations, as well as emerging immunotherapy treatment options.
Favorable Outcomes With Triplet Combinations
Currently, several doublet and triplet treatment options are recommended by the National Comprehensive Cancer Network for patients with relapsed/refractory multiple myeloma. Recent data, however, show superior outcomes with triplet combinations.
The phase III TOURMALINE study, for example, showed improved PFS rates with a triplet combination of the proteasome inhibitor ixazomib (Ninlaro), lenalidomide (Revlimid), and dexamethasone compared with placebo, lenalidomide, and dexamethasone in patients with relapsed/refractory multiple myeloma.1
Of the randomized 772 patients, the median PFS was 20.6 months in the ixazomib arm versus 14.7 months in the placebo arm (HR, 0.74; 95% CI, 0.587-0.939; P
= .01). Additionally, the rate of serious adverse events was similar between both arms (47% vs 49%, respectively).
Likewise, the phase III CASTOR study randomized 498 patients with relapsed/refractory multiple myeloma to receive daratumumab (Darzalex), bortezomib (Velcade), and dexamethasone or bortezomib and dexamethasone alone.2
After a median follow-up period of 7.4 months, the median PFS was not yet reached for the daratumumab arm versus 7.2 months for the doublet combination (HR, 0.39; 95% CI, 0.28-0.53; P
<.001). Higher rates of thrombocytopenia and neutropenia, however, were noted in the daratumumab group.
“Continuing with the theme…the 3 drugs here are better than the 2 drugs for PFS,” Mailankody said.
In the single-arm phase Ib EQUULEUS study, daratumumab plus pomalidomide (Pomalyst) and dexamethasone showed promise in patients with relapsed/refractory multiple myeloma with ≥2 prior lines of therapy (n = 103) with an ORR of 60%.5
Of the responders, 29% were MRD-negative.
Based on this trial, the FDA approved the combination for patients with relapsed/refractory who have received ≥2 prior lines of therapy including a proteasome inhibitor and lenalidomide.
Early Data Show Promise for CAR T-cell Therapies
In the CRB-401 phase I study of bb2121 CAR T-cell therapy, 21 adults with relapsed/refractory multiple myeloma received bb2121 in 4 cohorts in the dose-escalation portion of the trial.3
The overall response rate (ORR) in 18 evaluable patients receiving doses ≥150 x 106
was 94%. Additionally, 56% (n = 10) of patients achieved a complete response. Of the responders, 9 out of the 10 were minimum residual disease (MRD)–negative.
Bb2121 is a second-generation CAR T-cell therapy, developed by bluebird bio, targeting B-cell maturation antigen (BCMA) to redirect T cells to recognize and kill malignant myeloma cells, Mailankody explained.
“[These data are from the 2017 ASH Annual Meeting], showing very high response rates for patients who were treated at ≥150 x 106
. A side point that at the 50 x 106
mark, there is very little or no activity,” he added. From the preliminary findings, doses of 150 to 450 x 106
CAR T cells were selected for an expansion phase.
Based on updated data presented at the 2018 ASCO Annual Meeting, evaluable patients had a median progression-free survival (PFS) of 11.8 months at active doses ≥150 x 106
Of those who achieved MRD-negativity (n = 16), a median PFS of 17.7 months was seen.
“The mere fact that we are able to get 16 out of 43 patients to MRD-negative levels with a single CAR T-cell [treatment] in this setting is certainly quite remarkable,” Mailankody said. “The fact that we now have patients who are 1.5 to 2 years out without needing any additional treatment…is quite remarkable. I think it speaks to why there is so much enthusiasm and so many different trials from different companies that are ongoing in this space currently.”