Current treatment of newly diagnosed multiple myeloma involves lenalidomide maintenance therapy given until disease progression. The appropriate duration of maintenance therapy with lenalidomide has been unclear.
In this phase 3 trial, we enrolled patients with standard-risk newly diagnosed multiple myeloma who were not undergoing up-front autologous stem-cell transplantation. After induction treatment with a proteasome inhibitor???lenalidomide combination, patients were randomly assigned to receive indefinite-duration (continuous) lenalidomide or fixed-duration lenalidomide (for 2 years). The primary end point was overall survival; the trial had 80% power to detect a 50% increase in median survival (from 5 years to 7.5 years), with a two-sided alpha level of 5%, 395 patients undergoing randomization, and 204 deaths occurring during 9 years of follow-up. Research Summary Continuous or Fixed-Duration Maintenance Therapy in Multiple Myeloma
the end of induction, 516 patients were randomly assigned to the indefinite-duration group (260 patients) or the fixed-duration group (256 patients). a median follow-up of 86 months, overall survival did not differ significantly between the groups. With 80 deaths in each group, overall survival 7 years was 68.6% in the indefinite-duration group and 69.0% in the fixed-duration group (difference, ???0.4 percentage points; 95 confidence interval [CI], ???9.0 to 8.3; P=0.93). Progression-free survival 7 years was 36.1% in the indefinite-duration group and 29.7% in the fixed-duration group (difference, 6.4 percentage points; 95% CI, ???2.6 to 15.4). The 5-year cumulative incidence of second primary cancers, excluding nonmelanoma skin cancer, was 11.2% with indefinite-duration lenalidomide and 8.3% with fixed-duration lenalidomide. More adverse events occurred with indefinite-duration lenalidomide; the incidence of nonhematologic events of grade 3 or higher was 48.2% with indefinite-duration therapy and 31.5% with fixed-duration therapy.
In this phase 3 trial involving patients with standard-risk newly diagnosed multiple myeloma who were not undergoing up-front autologous stem-cell transplantation, indefinite-duration maintenance therapy after induction therapy did not result in significantly longer overall survival than fixed-duration maintenance therapy. (Funded by the National Cancer Institute of the National Institutes of Health and Amgen; ENDURANCE ClinicalTrials.gov number, NCT01863550.)
It comes as no surprise that bispecific agents are moving up into earlier lines of therapy in multiple myeloma. Here, in the setting of early relapsed, anti-CD38 and –imid exposed patients, single agent teclistimab showed an 18mo progression-free survival benefit over PFd/Kd.
Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma
This is a very impressive signal in a notoriously difficult population—seeing a 79% response rate and median progression-free survival (PFS) of 15.4 months in true extramedullary, triple-class–exposed myeloma is better than expected. Toxicity is real and management-intensive, but the depth and durability of response make this dual-bispecific approach feel like a meaningful advance.
CAR-T therapy outperformed standard of care (SOC) as a second-line treatment, with progression-free survival (PFS) not reached in the CAR-T group compared to 6.2 months in the SOC group. Despite two-thirds of patients crossing over, CAR-T still demonstrated a three-year overall survival rate of 63%, versus 52% with SOC. These are impressive and durable results. The SOC regimen consisted of three cycles of chemoimmunotherapy followed by high-dose chemotherapy and autologous stem cell transplant. This positions CAR-T as a viable second-line option for eligible patients.
Guess who’s coming as an option beyond AI (OBI)? Yes—this study showed no safety concerns and demonstrated comparable efficacy.