Bortezomib-based regimen + transplant increased progression-free survival in primary plasma cell leukemia

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Optimize induction phase

The study by Dr. Royer and associates is the first prospective trial to confirm that bortezomib-based regimens combined with a transplantation program may be effective and feasible in a significant proportion of patients with primary plasma cell leukemia. Response to induction therapy, however, was not remarkable; thus, although both cyclophosphamide and doxorubicin have demonstrated efficacy in primary plasma cell leukemia, the introduction of lenalidomide and/or incorporation of newer agents such as pomalidomide, carfilzomib, or daratumumab could hopefully optimize the induction phase and increase the rate and quality of response in future studies.

Hopefully, sequential phases of induction therapy, multiple transplantations (if applicable), further consolidation, and maintenance should ensure rapid disease control and reduction of early deaths from initial complications, a contrasting of clonal evolution that may induce drug resistance, and activity on residual disease by decreasing the risk of relapse. Feasibility of these approaches, however, may be limited, especially for older and frail patients who are unable to tolerate intensive induction or prolonged treatments. Personalized therapies with acceptable toxicities should be considered for these patients.

Dr. Pellegrino Musto is at Referral Cancer Center of Basilicata, Rionero in Vulture, Italy. He reported receiving honoraria from Celgene, Janssen-Cilag, Novartis, Sanofi, and Bristol-Myers Squibb. These comments are from an editorial (J Clin Oncol. 2016 Apr 25. doi: 10.1200/JCO.2016.66.6115) that accompanied the published study.




In a prospective study of 40 patients with primary plasma cell leukemia, upfront autotransplantation followed by allotransplant for younger patients and by consolidation/maintenance for older patients was associated with a median overall survival of 36.3 months and a median progression-free survival of 15.1 months.

Patients with this aggressive form of multiple myeloma received a regimen that combined standard chemotherapy, a proteasome inhibitor, high-dose melphalan followed by autologous stem cell transplantation, and allogeneic transplantation or immunomodulatory drugs, reported Dr. Bruno Royer of University Hospital in Amiens, France, and his associates.

Induction therapy consisted of four 21-day cycles: Cycles 1 and 3 included subcutaneous bortezomib, intravenous pegylated doxorubicin, and oral dexamethasone; cycles 2 and 4 included subcutaneous bortezomib, oral cyclophosphamide, and oral dexamethasone. Of 39 patients – one patient died 24 hours after study inclusion – 35 completed the four cycles. The overall response rate to induction was 69%: 10% of patients had a complete response and 26% had a very good partial response. Of 27 responding patients, 25 underwent high-dose melphalan followed by autologous stem cell transplantation.

The high response rates allowed 16 patients who were younger than 66 years and had an HLA-matched donor to then receive high-dose melphalan followed by autologous stem cell transplantation followed by consolidation with either an reduced-intensity conditioning allograft or a second high-dose melphalan followed by autologous stem cell transplantation and subsequent maintenance with lenalidomide, bortezomib, and dexamethasone for 1 year, the researchers said (J Clin Oncol. 2016 Apr 25. doi: 10.1200/JCO.2015.63.1929).

A total of 20% of patients had a complete response to the entire treatment protocol, 13% had a stringent complete response, 26% had a very good partial response, 5% had stable disease, and 5% had progressive disease. Thirteen patients died of progressive disease and four died of infections, including three that occurred during induction or after allograft.

This is only the second prospective trial in patients with primary plasma cell leukemia, an aggressive form of multiple myeloma that accounts for 2%-4% of cases, the researchers said. Future prospective trials should seek to optimize induction with newer combinations, such as carfilzomib, lenalidomide, dexamethasone, or monoclonal anti-CD38 antibodies. Also, optimizing the stem cell conditioning procedure and the postallograft immunomodulation may further benefit younger patients.

Dr. Royer reported receiving honoraria from Amgen and having served as a consultant or advisor for Octapharma Plasma. Fifteen coinvestigators also reported financial relationships with a number of pharmaceutical companies.

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