Blood cancers

Induction therapy response can’t stratify MM patients away from ASCT

Depth of response to induction therapy is likely not sufficient to identify patients who can defer autologous stem cell transplantation (ASCT) in multiple myeloma, a new study finds.

Patients with certain characteristics may have good outcomes with deferred ASCT, but the study was too small to make firm conclusions.

“The benefit of ASCT is related to an uplift in major response and minimal residual disease (MRD) negativity, associated with improved progression‐free survival (PFS) and overall survival (OS),” wrote study authors led by Dr Rakesh Popat, of University College London Hospitals, in the British Journal of Haematology. “Achieving this with induction chemotherapy alone questions the additional benefit of upfront ASCT.”

The new PADIMAC trial was a phase II study where patients who achieved a major serological response (at least a very good partial response, or VGPR) to induction therapy were stratified to receive no further treatment until disease progression, when ASCT could be offered.

Of 153 total patients, the overall response rate following induction therapy was 82.4%, and the 126 patients who responded went to peripheral blood stem cell harvest (PBSCH). Of those, 63 patients (41.2%) achieved VGPR.

After a median of 71.4 months from PBSCH, the median PFS was 17.0 months in the VGPR group, compared with 19.6 months in the patients who went on to ASCT. The two-year PFS rate was 37.1% and 33.3%, respectively (p = .36).

Within the VGPR group, patients who were MRD-negative at day 100 had a median PFS of 24.8 months, while those who were MRD-positive had a PFS of only 9.9 months.

Of the 63 VGPR patients, 24 died, 33 progressed and remain alive, and six are alive without progression. The two-year OS rate for the group was 91.9%.

“Our findings suggest that using serological response alone was not adequate to stratify patients, as many in ≥VGPR remain MRD‐positive, with short PFS indicating that further cytoreductive therapy is required,” the authors concluded. “Deferred ASCT may, however, be an option for standard risk MRD‐negative patients, warranting further investigation.” They recommended that MRD-positive patients post-induction should receive ASCT, as the non-ASCT pathway outcomes were poor.

“Future trials that employ MRD status and cytogenetic risk to stratify patients will help identify patients that can safely be allocated a no‐ASCT pathway,” they wrote. “Such efforts are especially pertinent today, when the risks associated with the COVID‐19 pandemic highlight the need for such a pathway.

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