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Autologous HSCT underused despite survival benefits for newly diagnosed multiple myeloma
Autologous hematopoietic stem cell transplant extends survival for individuals with newly diagnosed multiple myeloma but is used infrequently for this patient population, according to findings published in Journal of the National Cancer Institute.
Debate exists in the oncology community about whether autologous HSCT should be used for patients with myeloma, as well as how transplant candidates should be chosen.
Aaron S. Rosenberg, MD, MS, assistant professor in the division of hematology and oncology at UC Davis Comprehensive Cancer Center, and colleagues used the California Cancer Registry to identify 13,494 patients diagnosed with myeloma between 1998 and 2012.
Approximately one in five (20.8%) underwent autologous HSCT (median time to transplant, 9.4 months).
Median OS for those who underwent autologous HSCT was 72.9 months (95% CI, 68-78).
Researchers observed improved OS with autologous HSCT at any time (djusted HR = 0.83; 95% CI, 0.75-0.92). However, patients who underwent autologous HSCT more than 1 year after diagnosis achieved shorter OS (adjusted HR = 1.33; 95% CI, 1.16-1.51).
HemOnc Today spoke with Rosenberg about the implications of these study results, why autologous HSCT may be underutilized for individuals with newly diagnosed myeloma, and what can be done to educate members of the clinical community that transplant remains a viable, effective option for this patient population.
Question: How did this study come about?
Answer: Since 2010, there have been ongoing debates at national meetings about the role of autologous HSCT for patients with multiple myeloma. This has been a standard approach for fit patients aged younger than 65 years for quite some time. Data from Attal and colleagues in 1996 showed an OS benefit with early transplant. However, since then, the FDA has approved multiple new classes of drugs that are well-tolerated and more effective than chemotherapy regimens used in the 1990s. This has led to an ongoing debate about whether autologous HSCT is still necessary and useful for these patients.
Three randomized trials looked at the use of early vs. later transplant for predominantly European populations. These studies showed consistent PFS benefit with the use of early transplant. Two studies showed an OS benefit, but one did not. This study used what would be considered a standard regimen for newly diagnosed patients in the United States, and this fueled the debate about whether we need to give patients transplant referrals.
One major criticism is that these studies were conducted in Europe, not in the U.S., where standard treatment for newly diagnosed patients is somewhat different. A question remains about how we use transplant in the U.S. and how we should apply the results to our patients — especially because we have more drugs available and can use them in different combinations and in a slightly more liberal fashion than in Europe.
Q: How did you conduct the study?
A: We sought to determine if transplant is still useful for patients with multiple myeloma, especially with regard to OS. We looked at the approval and utilization of all drugs available during the late 1990s through 2012 to determine if transplant still has a role.
We linked the California Cancer Registry to the statewide hospital discharge database in California, which provides information about every admission at non-VA hospitals in California. We compared patients based on several factors — such as age, socioeconomic status, race/ethnicity and comorbidities — that contribute to the decision about whether to use transplant. We also assessed OS.
Q: What did you find?
A: We observed a 17% decreased risk for death among patients who underwent transplant. This did not differ by era. If newer therapies were rendering transplant obsolete, one would expect to see a decreased association between transplant and survival in more recent eras. Because we saw the opposite, this means transplant continues to have a role in the treatment of these patients. We also performed an analysis in which patients who underwent transplant were matched to controls. Controls had to live at least as long as it took their matched counterparts to undergo transplant. We calculated the average survival from transplant or from the time the patient would have undergone transplant had they been in the transplant group. Median OS after transplant was nearly 73 months in the transplant group and nearly 48 months among controls.
Q: What are the clinical implications of the findings?
A: We were surprised so few patients underwent transplant. Even among those aged younger than 60 years, only 38% underwent transplant. Transplant is still relevant to try to keep patients with newly diagnosed myeloma alive longer, and we also need to do a better job getting this information to the health care community so physicians can send patients for referral. We need to do a better job selling this to patients, too. This is not an easy procedure to undergo, but the benefits are well worth it.
Q: Why is autologous HSCT underutilized in this patient population?
A: We do not know. In an abstract published during the ASH Annual Meeting and Exposition 2 years ago, we looked at socioeconomic and ethnic barriers to transplant. Results showed black patients are much more likely to receive transplant. This has not been recapitulated in other databases, so barriers likely are regional. The low transplant rate may be due, in part, because some people believe we have moved past transplant. This is not necessarily data driven. There also is a misconception that we cannot transplant patients aged older than 65 years, so these patients are not sent for an evaluation. However, this is not true, either. Older patients have benefited from transplant.
Q: What should be done to help the clinical community understand that transplant remains a viable, effective option?
A: I hope research like this will help get the message out. A lot of the academic centers also are transplant centers. By and large, the thought leaders who are giving the invited lectures are still saying that transplant has a role. It is interesting to me to know that this is not well-implemented. – by Jennifer Southall
References:
Attal M, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1611750.
Attal M, et al. N Eng J Med. 1996;doi:10.1056/NEJM199607113350204.
Gay F, et al. Lancet Oncol. 2015;doi:10.1016/S1470-2045(15)00389-7.
Palumbo A, et al. N Engl J Med. 2014;doi:10.1056/NEJMoa1402888.
Rosenberg AS, et al. Blood. 2016;128:846.
Rosenberg AS, et al. J Natl Cancer Inst. 2018;doi:10.1093/jnci/djy073.
For more information:
Aaron S. Rosenberg, MD, MS, can be reached at UC Davis Comprehensive Cancer Center, 4501 X St., Suite 3016, Sacramento, CA, 95817; email: asrosenberg@ucdavis.edu.
Disclosure: Rosenberg reports no relevant financial disclosures.