Bortezomib to Treat Multiple Myeloma

Chicago—In a randomized, multicenter phase 3b trial, 3 bortezomib-based therapies had similar rates of progression-free survival and were active in treating patients with newly diagnosed multiple myeloma (MM) who were ineligible to receive high-dose chemotherapy and stem cell transplantation (HDTSCT). The findings were presented at the ASCO meeting in a poster titled Impact of Baseline Characteristics on Efficacy and Safety after Bortezomib-Based Induction and Maintenance in Newly Diagnosed Multiple Myeloma Patients Ineligible for Transplant in the Phase 3b UPFRONT Study. The authors noted elderly patients are not typically eligible for HDT-SCT because of their age, comorbidities, and toxicity. They hypothesized that bortezomib-based therapies could be an alternative to HDT-SCT and a first-line therapy. Several phase 2 and phase 3 trials found regimens that included bortezomib showed activity in newly diagnosed MM patients, although this trial was the first to compare the safety and effectiveness of bortezomib-based treatments. The regimens were bortezomib and dexamethasone (BD); bortezomib, thalidomide, and dexamethasone (BTD); and bortezomib, melphalan, and prednisone (BMP). There were 100 patients in each of the 3 arms. Inclusion criteria in the UPFRONT (Untreated Patients Receiving Therapy for Multiple Myeloma in a Randomized Trial of Three Novel Regimens for Patients Not Intending to Receive Transplant Therapy) study included ≥18 years of age, ineligibility for HDT-SCT, Karnofsky Performance Status scale score ≥50%, symptomatic MM or asymptomatic MM with evidence of organ involvement, and measurable disease requiring systemic therapy. Patients were excluded if they had grade ≥2 peripheral neuropathy within 21 days before enrollment. The trial consisted of eight 21-day cycles in the induction phase in which the 3 groups received their assigned medications at regular intervals, followed by five 35-day maintenance cycles in which each group took 1.3 mg/m2 of bortezomib at day 1, 8, 15, and 22 of each cycle. Patients in the BD, BTD, and BMP groups received a median of 9, 6, and 7 cycles, respectively. In addition, 56% of the BD group received maintenance therapy compared with 33% in the BTD group and 43% in the BMP group. In each arm, patients receiving maintenance therapy had a better response compared with those who only had the induction therapy: 71% versus 68% in the BD group, 79% versus 78% in the BTD group, and 73% versus 71% in the BMP group. At a median follow-up of 18.8 months, the median progression-free survival was 14.2 months, 14.9 months, and 17.2 months for the BD, BTD, and BMP groups, respectively (P=.3381). The authors indicated a longer follow-up period was necessary to confirm the results. A subgroup analysis found the rates of very good partial response and postinduction complete response/near-complete response were significantly higher in patients <75 years of age compared with patients ≥75 years of age (P=.0344 and P=.0127, respectively). In addition, patients in the BTD group had the highest rates of total adverse events (AEs), grade ≥3 AEs, serious AEs, and study discontinuations due to AEs. The rates of peripheral neuropathy were significantly lower in males compared with females (P=.0353) and in white patients compared with nonwhite patients (P=.0302).