First line regimen, first quad for transplant INELIGIBLE patients, PFS at 5 years is 63% vs 45% for RVD. This will probably be the new standard of care for this population with manageable toxicity. Recall Dara RVD is for transplant eligible patients.
Bortezomib, lenalidomide, and dexamethasone (VRd) is a preferred first-line treatment option for patients with newly diagnosed multiple myeloma. Whether the addition of the anti-CD38 monoclonal antibody isatuximab to the VRd regimen would reduce the risk of disease progression or death among patients ineligible to undergo transplantation is unclear.
In an international, open-label, phase 3 trial, we randomly assigned, in a 3:2 ratio, patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation to receive either isatuximab plus VRd or VRd alone. The primary efficacy end point was progression-free survival. Key secondary end points included a complete response or better and minimal residual disease (MRD)–negative status in patients with a complete response.
A total of 446 patients underwent randomization. At a median follow-up of 59.7 months, the estimated progression-free survival at 60 months was 63.2% in the isatuximab-VRd group, as compared with 45.2% in the VRd group (hazard ratio for disease progression or death, 0.60; 98.5% confidence interval, 0.41 to 0.88; P<0.001). The percentage of patients with a complete response or better was significantly higher in the isatuximab-VRd group than in the VRd group (74.7% vs. 64.1%, P=0.01), as was the percentage of patients with MRD-negative status and a complete response (55.5% vs. 40.9%, P=0.003). No new safety signals were observed with the isatuximab-VRd regimen. The incidence of serious adverse events during treatment and the incidence of adverse events leading to discontinuation were similar in the two groups.
Isatuximab-VRd was more effective than VRd as initial therapy in patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation. (Funded by Sanofi and a Cancer Center Support Grant; IMROZ ClinicalTrials.gov number, NCT03319667.)
This regimen vs pomalidomie, bortezomib and dexma. 12-month estimated progression-free survival with BPd was 71% compared with 51% with PVd (hazard ratio for disease progression or death, 0.52) Ocular toxicity Grade 3 or higher adverse events occurred in 94% of the patients in the BPd group and 76% of those in the PVd group.
This regimen vs Daratumamab, bortezomib and dexa. Median progression-free survival was 36.6 months in the BVd group and 13.4 in the DVd Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. Again higher ocular toxicity but manageable with dose adjustment and supportive therapy. Those trials may be the come back for Belantamab.
Triplet second line therapy shows superiority over daratumumab bortezomib and dexamethasone. This regimen is now used in first line with lenalidomide in some patients as quadruplet therapy, hence this second line regimen with Blantamab could be a second line option. The eye exam is still a pain and it is also more toxic.
CAR-T for myeloma, impressive response rate, overall survival not reached.
The Bi-specific antibody era has started full-force with impressive results and reasonable toxicities, in different hematological neoplasms. Community oncology adoption of Bi-specific antibody will be successful, once standard operating procedures are in place, and multidisciplinary training takes place insofar as management of CRS. I am optimistic as to the uptake of this class of drugs in 1-2 years, pending payer coverage issues.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
