Improved outcomes for patients with multiple myeloma (MM) following autologous stem cell transplantation (ASCT) require more precise response rates for use in clinical trials of this disease because marked differences are apparent.
Achieving a sustained complete response (CR) for a decade or more is no longer a rarity. Since the development of subcategories of CR by the International Myeloma Working Group (IMWG), some ambiguities have been eliminated and clinicians now have a better understanding of prognostic factors. There currently are three levels of successful treatment: stringent CR (sCR), CR (i.e., standard CR) and nCR (near CR). Near CR describes patients with less than 5% bone marrow plasma cells (BMPCs) and monoclonal protein detected by urine immunofixation only. Standard CR was defined as patients having no soft tissue plasmacytomas, absence of monoclonal proteins by electrophoresis or immunofixation and having less than 5% BMPCs. Stringent CR was defined as patients with a normalized free light-chain ratio (κ/λ range, 0.26-1.65) in the absence of monoclonal BMPCs. Other categories used by the IMWG for lesser degrees of response include progressive disease, stable disease, partial remission and very good partial response.
Between 2002 and 2008, the researchers prospectively followed 445 consecutive patients with MM who underwent ASCT within a year of diagnosis. The Mayo Clinic researchers, who published their findings in the Journal of Clinical Oncology (2013;31:4529-4535, PMID: 24248686), focused attention on those patients who attained some level of CR: 109 (25%) sCR, 37 (8%) CR and 91 (20%) nCR.
The authors determined that when data for patients achieving sCR were separated from the total pool of patients with a positive response, five-year overall survival (OS) rates were 80% (sCR), 53% (CR) and 47% (nCR), respectively. Median time to progression for patients achieving sCR was 50 months compared with 20 and 19 months for CR and nCR, respectively). This study suggests a commonality between the patients achieving nCR and CR, and that the sCR status is worth regarding as a distinctly superior and separate outcome. A post-ASCT response of sCR was found to be an independent prognostic factor for survival, as were proliferation rate, pre-ASCT cytogenetics and performance status.
Amrita Y. Krishnan, MD, FACP|
Director, Multiple Myeloma Program
Associate Director, Medical Education & Training,
Hematology & Hematopoietic Cell Transplantation
City of Hope
The paper by Kapoor and colleagues highlights the question, “How low can you go and does it matter?” Not surprisingly, in many malignancies there is a strong correlation between achieving a CR and OS. In fact, one of the early benefits of high-dose chemotherapy and ASCT was the ability to achieve high response rates and good depth of response in patients, which translated into improved survival.1 The introduction of novel agents into induction therapy has led to higher responses both pre- and post-transplant. Indeed, with the newest induction regimens, as many as 50% of patients may achieve a CR.2
The present study suggests that perhaps we should aim even higher in our response goals—that is, attempt to attain sCR. In this series of 445 prospectively followed patients who underwent ASCT, those who attained an sCR as best response at any time post-transplant had better five-year OS compared with those who achieved CR or nCR.
The study suffers from the fact that a variety of induction regimens were chosen and that there is no complete assessment of maintenance therapy. The authors noted, “Maintenance therapy was generally not used after ASCT.” However, we do know from the CALGB 100104 trial that maintenance with lenalidomide post-ASCT improved OS,3 so we cannot discount the effect of maintenance on a subgroup of patients. Other methods for assessment of disease, such as magnetic resonance image or positron emission tomography scanning, were not done, and might provide another important variable for survival. Results from toxicity analyses and quality-of-life assessments also would be informative. Nonetheless, the results of this study are intriguing and suggestive that sCR may be the new end point, to be achieved with a combination of novel agents in induction, followed by ASCT.
- Lahuerta JJ, Mateos MV, Martinez-Lopez J, et al. Influence of pre- and post-transplantation responses on outcome of patients with multiple myeloma: sequential improvement of response and achievement of complete response are associated with longer survival. J Clin Oncol. 2008;26:5775-5782, PMID: 19001321.
- Richardson P, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy for patients with newly diagnosed multiple myeloma. Blood. 2010;116:679-686, PMID: 20385792.
- McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1770-1781, PMID: 22571201.
Dr. Krishnan reported no relevant financial disclosures.