|LETTER TO EDITOR
|Year : 2019 | Volume
| Issue : 2 | Page : 270-271
Multiple myeloma: The paradox and the challenge
Hasmukh Jain1, Jayashree Thorat2, Neha Sharma3
1 Department of Medical Oncology, Clinical Trial Co-ordinator, Tata Memorial Hospital; Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
2 Department of Medical Oncology, Clinical Trial Co-ordinator, Tata Memorial Hospital, Mumbai, Maharashtra, India
3 Department of Clinical Research, Clinical Trial Co-ordinator, Tata Memorial Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||20-Dec-2019|
Department of Medical Oncology, Tata Memorial Hospital, Mumbai - 400 012, Maharashtra; Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Jain H, Thorat J, Sharma N. Multiple myeloma: The paradox and the challenge. Cancer Res Stat Treat 2019;2:270-1
Multiple myeloma constitutes 10% of hematological malignancies. In the 90s, the median survival was 2–3 years. The outcomes have improved, such that 20%–30% of patients live beyond 10 years. Bagal and Bonda have comprehensively summarized the principles of treatment, the current treatment options and given a glimpse of what lies in store in this field of myeloma. We would like to highlight a couple of points. The design of clinical trials in myeloma and the choice of surrogate endpoints are a topic of debate. Overall survival (OS) is the most meaningful and objective endpoint. An improvement in OS is what matters the most to the patient, provided the quality of life is preserved. None of the recent clinical trials with the newer drugs have used OS as a primary endpoint. OS in myeloma is affected by the numerous salvage therapy options and the presence of competing causes of death such as comorbidities. An interesting paradox is that the availability of newer drugs has made it difficult to conduct a clinical trial with OS as an endpoint. Since the survival has improved progressively, any trial to test an improvement in OS needs to run for at least 8–10 years to detect meaningful differences, for instance, CALGB 100104 trial. By the time the trial is complete, there is a possibility that the research question is irrelevant. This brings us to the question of what is an ideal surrogate endpoint? For most of the trials, progression-free survival (PFS) is used as the endpoint. This is based on a meta-analysis that demonstrated a moderate to strong correlation between the PFS and OS. Nevertheless, this analysis was not based on individual patient-level data. From our earlier experience, we know that an improvement in PFS does not always translate into an OS benefit, the maintenance trial with thalidomide being a case in point. There is an attempt to use the minimal residual disease as an endpoint. As highlighted by Bagal et al. in the review, at present, this is at best a prognostic marker, with several issues such as the need for standardization and validation before it is used as an endpoint to test new drugs.
The enthusiasm surrounding the newer drugs needs to be tempered with the realities of our situation. Autologous stem cell transplant (ASCT) and novel agents (IMiDs and proteasome inhibitors [PIs]) drove the improvement in outcomes seen in the late 90s and beyond. The newer agents are further improving the outcomes., The question is how much has this impacted care in our region? Jacob et al. published the results of their myeloma cohort (389 patients) treated between 2005 and 2016 and the ASCT rates were a dismal 6%. Bortezomib was used in 24% and lenalidomide in 3% of patients. Kumar et al. reported their results of the transplanted cohort (349 patients); only 22% had received lenalidomide and 29% received PIs. The availability of treatment options in the literature is one thing, but the ability to deliver it to the majority requiring them and not a select few is another thing. The novel agents are unlikely to have a different fate at least in the immediate future. Drugs such as daratumumab that require to be administered indefinitely till progression or intolerance will probably have even lower rates of acceptance despite their phenomenal activity.
There is a need to develop newer drugs, but more importantly, make them available to the majority of the patients. The AIDS story gives us hope that it is possible.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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