Autotransplant with and without induction chemotherapy in older multiple myeloma patients: long-term outcome of a randomized trial

Abstract

Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of induction chemotherapy cycles is still unclear. A total of 434 patients aged 60-70 years were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction. For all patients, double autologous transplantation after melphalan 140 mg/m2 (MEL140) was planned. The primary end point was progression-free survival. Of 420 eligible patients, 85% received a first transplant and 69% completed double transplantation. Treatment duration was short with a median of 7.7 months with induction chemotherapy cycles and 4.6 months without induction. On an intention-to-treat basis, median progression-free survival with induction chemotherapy cycles (207 patients) was 21.4 months versus 20.0 months with no induction cycles (213 patients) (hazard ratio 1.04, 95% confidence interval 0.84-1.28; P=0.36). Per protocol, progression-free survival was 23.7 months versus 23.0 months (P=0.28). Patients aged 65 years or over (55%) did not have an inferior outcome. Patients with low-risk cytogenetics [absence of del17p13, t(4;14) and 1q21 gains] showed a favorable overall survival and included the patients with sustained first remission. MEL140 was associated with a low rate of severe mucositis (10%) and treatment-related deaths (1%). Based on hazard ratio, the short treatment arm consisting of mobilization chemotherapy and tandem MEL140 achieved 96% of the progression-free survival, demonstrating its value as an independent component of therapy in older patients with multiple myeloma who are considered fit for autologous transplantation. (clinicaltrials.gov identifier: 02288741).

Trial registration: ClinicalTrials.gov NCT02288741.

Copyright© Ferrata Storti Foundation.

Figures

Figure 1.

Study design and consort diagram. (A) Study design. Patients were randomized (R) to the two study arms: 1) induction chemotherapy cycles; and 2) no induction cycles. (B) Consort diagram. Inclusion, randomization, treatment and follow up of enrolled patients. PBSCs: peripheral blood stem cells; ICC: induction chemotherapy cycles; Dex: dexamethasone; Mob: mobilization chemotherapy; MEL140: high-dose melphalan.

Figure 2.

Long-term outcomes after randomization between induction chemotherapy cycles and no induction cycles. The curves for progression-free survival with induction chemotherapy cycles versus no induction cycles are shown based on intention-to-treat (A) and per protocol (tandem transplants) (B).

Figure 3.

Outcome for age and cytogenetic risk groups. The curves for progression-free survival and overall survival are shown for (A) the age groups 60–64 years and 65–70 years, and (B) for high-risk, intermediate-risk and low-risk cytogenetics.