Post-ASH 2018: MRD Evaluation of Patients with Multiple Myeloma Who Receive Bortezomib Consolidation after Frontline Tandem Transplantation

Poster presentation by Dr. Richard LeBlanc

This phase II study evaluates the impact of bortezomib as a first-line treatment administered in consolidation after a tandem autologous transplant approach, followed by an allogeneic hematopoietic stem cell transplant in young or at-risk patients with multiple myeloma (MM).

Previously published data (Ahmad I. et al., BMT 2016;51:529-535) demonstrate that with a median follow-up of 8.8 years, this tandem approach without bortezomib consolidation produces an estimated 10-year progression-free survival (PFS) of 41%. On the other hand, two problems are observed: 1) post-allogeneic transplant recurrences remain frequent at nearly 50%, and 2) the incidence of chronic graft versus host disease (GvHD) is frequent at around 80%. This study proposes the use of bortezomib in consolidation in order to reduce these two problems and improve outcomes.

Patients eligible for the study had high-risk biological or clinical factors or were ≤50 years old regardless of the risk. Forty patients with MM were recruited, including 39 evaluable patients. The median age was 54 years old, 41% of patients had an International Staging System of 3, and 65% of patients had unfavourable genetics, including 18% with at least two abnormalities (ultra high-risk). Cyclophosphamide with bortezomib and dexamethasone (82%) and bortezomib with thalidomide and dexamethasone (18%) were used as induction treatment for a median of 4 cycles. Forty-one percent of patients received a related allogeneic transplant and 59% an unrelated one. Bortezomib could be administered at 96.4% of the expected doses. Bortezomib proved to be safe and well tolerated after the allogeneic transplant.

The responses to each phase of treatment gradually improved. Complete response (CR) was observed in 57% of patients after autologous transplant, 62% after allogeneic transplant, and 83% after the addition of bortezomib. Immunophenotypic CR (sCR with minimal residual disease [MRD] negativity) was observed in 21% of patients after autologous transplant, 26% of patients after allogeneic transplant, and 63% of patients after the addition of bortezomib.

With a median follow-up of 24 months, the median PFS was 34 months with a 2-year PFS of 65% and a 2-year overall survival of 91%. The cumulative incidence of progression at 2 years was 29% with a cumulative incidence of non-relapse mortality of only 6%. The evaluation of MRD at 6 months after the initiation of bortezomib demonstrates a predictive value of the probability of progression. In fact, patients who tested MRD negative at that time had a significantly lower probability of progression than those who tested MRD positive.

The incidence of grade II–IV acute GvHD at 1 year was 27% and grade III/IV was 14%. The incidence of moderate-severe chronic GvHD at 2 years was 47% and severe GvHD was 9%. Compared to a control group with the same treatment regimen without consolidation of bortezomib, the incidence and severity of chronic GvHD were significantly lower.

In summary, this treatment regimen is safe and is associated with high-quality responses. The documentation of an MRD-negative test 6 months after initiating bortezomib is associated with a better clinical course. Particularly in a context where new treatment modalities are difficult to access, the use of this treatment regimen for young or at-risk patients may be considered.

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