PracticeUpdate Conference Series ASH 2018

Daratumumab Improves Outcomes in Fragile Patients With Multiple Myeloma Newly-diagnosed patients ineligible for transplant had greater progression-free survival and a lower risk of deathwith the addition daratumumab to standard therapy.

N ewly diagnosed multiple myeloma patients ineligible for transplant who receive daratu- mumab on top of standard lenalidomide and dexamethasone therapy are less likely to expe- rience disease progression or death relative to those receiving standard therapy alone, according to interim results of the phase III MAIA study. To compare the performance of daratumumab plus standard-of-care lenalidomide and dexametha- sone with that of lenalidomide and dexamethasone alone in multiple myeloma patients ineligible for autologous stem cell transplantation, researchers randomized 737 such patients from 14 countries 1:1 to each of two treatment arms and followed patients for disease progression and toxicity. The study was funded by Janssen, Inc., manufacturers of daratumumab. The primary endpoint was progression-free sur- vival (PFS). Secondary endpoints included safety, overall response rate, and minimal residual disease negativity rate. Patients included in the trial were ineligible for high-dose chemotherapy and autologous stem cell transplantation due to either advanced age (≥65 years old) or the presence of comorbidities. Among the 642 patients who had available kar- yotyping data, 86% were considered standard cytogenetic risk, whereas 14% were considered high cytogenetic risk. A total of 27% were at ISS stage 1, 43% were at ISS stage II, and 29% were at ISS stage III, respectively. Participating patients had ECOG scores between 0 and 2, with two-thirds having ECOG score ≥1 and 17% having ECOG score ≥2. Participants were

required to have creatinine clearance rates ≥30 mL/min. The median participant age was 73, with patients from 45 to 90 years old participating. As many as 44% of participating patients were over 75 years old. Baseline participant characteristics were balanced between trial arms, with patients from the United States, Canada, Australia, Israel, the United Kingdom, and several continental European countries. After 239 PFS events had occurred during a median follow-up of 28 months, the researchers performed a prespecified interim analysis, which revealed that patients in the daratumumab-con- taining arm experienced a 45% reduction in risk of progression or death relative to patients in the lenalidomide and dexamethasone arm (HR 0.55; 95% CI 0.43–0.72, P < .0001). Whereas median PFS was 31.9 months in the lenalidomide and dex- amethasone arm, median PFS was not reached in the daratumumab-containing arm. As many as 47.6% of patients in the daratumumab plus lenalidomide and dexamethasone arm expe- rienced a complete response, whereas 24.7% of patients in the lenalidomide/dexamethasone arm did so (odds ratio [OR] 2.75, P < .0001). Similarly, as many as 79.3% of patients in the daratumum- ab-containing arm experienced a very good partial response or better, whereas only 53.1% of those in the arm without daratumumab did so (OR 3.4, P < .0001). At the time of the interim analysis, a total of 19% of patients had died, with a hazard ratio for overall survival of 0.78 trending to favor daratumumab (95% CI 0.56–1.1).

Dr. Thierry Facon

PRACTICEUPDATE CONFERENCE SERIES • ASH 2018 18