Source: Multiple Myeloma – ASH Clinical News
In our March 2021 issue, we reported on findings from a review article examining disparities in outcomes among patients with multiple myeloma (MM), in which the authors found that Hispanic and non-Hispanic Black patients have certain characteristics that contribute to poorer survival than their white counterparts, but Hispanic patients tend to have higher overall survival (OS) due to increased use of frontline autologous hematopoietic cell transplantation (AHCT). Here, a hematologist continues the conversation on the growing body of literature drawing attention to the inequities in myeloma care.
With their study published in Clinical Lymphoma, Myeloma & Leukemia, Kaur et al. highlighted key themes hidden in the data. This retrospective study evaluated 939 eligible patients with a diagnosis of MM from a single center – Montefiore Medical Center Cancer Registry. The demographics included 30% Hispanic, 52% non-Hispanic Black, and 18% non-Hispanic white patients.
Median age for all patients was comparable to the known literature (65.6 years) with an average age of 64.5 years in Hispanic and Black patients, compared with 70.6 years in white patients. It was also noted the Hispanic and Black people were diagnosed younger, such that for individuals diagnosed under 60 years of age, 35.3% were non-Hispanic Black, 28.8% were Hispanic, and 16.5% were non-Hispanic white.
Surveillance Epidemiology and End Results (SEER) data have illustrated increased incidence of MM in minorities, depicting the highest incidence in Black people.
Highlighted in the study is increased renal dysfunction at the time of diagnosis, seen more among the minority patients (61.1% in Black, 56.4% in Hispanic, and 48.8% in white patients). In addition, the lactate dehydrogenase (LDH) levels were comparatively elevated in the Hispanic and Black populations than in the white patients.
Given the International Myeloma Working Group (IMWG) Revised International Staging System (R-ISS) criteria, this should translate to Hispanic and Black groups being diagnosed with higher stage or more aggressive disease. Yet, interestingly, the white patients in this analysis more often received triple-drug induction therapy than the minority groups. Also, the Hispanic and white patients more often underwent AHCT than Black patients.
Ultimately, the study found the longest median OS among Hispanic patients, at 110 months, followed by 69 months among white patients and 65 months among Black patients.1 The latter points to inequities in health care for Black patients.
Benjamin Derman, MD, wrote a compelling perspective accompanying the summary of these findings in ASH Clinical News, highlighting cost, access, and compliance to therapies as likely inadequate reasons for fully explaining these results. He suggests that younger age and AHCT more heavily affected the superior outcomes for the Hispanic group. Lack of information on cytogenetic abnormalities and therapies received for each group were also mentioned as drawbacks to the study, as well as its inherent retrospective nature.
In comparison, Dr. Derman and colleagues published a prospective observational Multiple Myeloma Research Foundation (MMRF) CoMMpass registry study evaluating 639 eligible patients in Blood Cancer Journal earlier last year. The similarities between this and the study by Kaur et al. are of interest.
In the report from Derman et al., the demographics evaluated 113 Black patients and 526 white patients. Similar to the previous study, it was noticed that Black patients were less likely to receive triple-drug induction compared with white patients (55% vs. 73%, respectively; p<0.001) and less likely to receive AHCT (39% vs. 49%; p=0.04).
This study also included a comparison of cytogenetic abnormalities between the groups. Researchers observed that, even with evidence of zero to one high-risk cytogenetic abnormality at diagnosis, 37% of Black patients received triple-drug induction versus 50% of white patients (p=0.02). For triple-drug induction and AHCT, the difference was 31% of Black patients versus 44% of white patients (p=0.01). At the level of two or more high-risk cytogenetic abnormalities, Black and white patients had similar rates of triple-drug induction and AHCT.2 On par with the previous study, the outcomes for Black patients were inferior to those for white patients.
These two studies accentuate the inequities in care among Black, Hispanic, and white patients. Each study carries its own characteristic flaws, but the common thread noted here indicates the existence of additional gaps in health care that need to be addressed. In my opinion, more prospective and retrospective studies such as these need to be performed to highlight to the academic, physician, and patient communities the impact of inequity in clinical care outcomes.
Socioeconomic factors, cost, compliance, and their surrogates do not fully explain the differences seen. Further evaluation both in physician practice and patient communities is needed to elucidate optimal solutions to address these discrepancies.
Monique Hartley-Brown, MD
Northwell Health Cancer Institute
New Hyde Park, New York
Kaur G, Mejia Saldarriaga M, Shah N, et al. Multiple myeloma in Hispanics: incidence, characteristics, survival, results of discovery, and validation using real-world and Connect MM registry data. [published online ahead of print, 2020 Nov 21]. Clin Lymphoma Myeloma Leuk. doi: 10.1016/j.clml.2020.11.013.
Derman B, Jasielec J, Langerman S, et al. Racial differences in treatment and outcomes in multiple myeloma: a multiple myeloma research foundation analysis. Blood Cancer J. 2020;10(8):80.
Dr. Derman’s response:
Dr. Hartley-Brown’s keen insights on racial and ethnic inequity and its impact on clinical outcomes in MM are representative of a growing understanding within patient and clinician circles of the need for more racially and socioeconomically inclusive approaches to clinical care. Attempts to use biology to solely describe racial disparities in cancer outcomes is fraught with a profound misunderstanding of the roles that socioeconomic status, access to care, bias, and racism play in the journey of a patient from diagnosis through treatment. With that said, myeloma represents an interesting case study as Black individuals have a two- to three-fold higher prevalence of the myeloma precursor condition monoclonal gammopathy of undetermined significance, along with a younger age at myeloma diagnosis, compared to white individuals. This suggests that there may in fact be some biologic component that leads to a predilection of the disease among Black patients.
We must look beyond biology. I am proud to work on the south side of Chicago – an often-discussed area of the city comprised of predominantly underserved Black patients – and to have the opportunity to narrow the gaps that exist for these very individuals. Most patients I see are acutely aware (as am I) that I do not look like them, which requires of me an even greater attention to overcome these obstacles.
What is troubling is that on a national and global scale, Black patients make up less than 5% of pivotal clinical trials in myeloma, despite comprising 20% of newly diagnosed MM cases.1 More inclusive clinical trial eligibility criteria such as less stringent absolute neutrophil and creatinine clearance cutoffs (both of which increase the chances of exclusion of Black patients) may help to increase the pool of eligible Black trial candidates.
But it will take more than that to overcome the complicated amalgamation of well-founded medical mistrust, clinician bias, and systemic issues that lead to their underrepresentation in clinical trials. Even outside of clinical trials, Black patients are less likely to receive standard-of-care triplet therapies and AHCT. Simply put, this needs to change.
We can take it a step further: How are we in the myeloma community to be sure that the risk prognostication schema we use (such as the ISS or R-ISS) are externally valid for patients who fall outside of the narrow clinical trial populations that were used to generate these scoring systems? We do not know if patients of different races and ethnicities, patients older than 65 years of age, and/or patients with suboptimal renal function have similar natural disease histories or responses to conventional therapies.
As a field, we have made great strides in myeloma diagnostics and therapies. They cannot only exist for the few. Now we must apply that same ingenuity toward tackling an even greater foe; resolving inequities such that all patients can enjoy these successes.
Benjamin Derman, MD
University of Chicago Medical Center
Bhatnagar V, Gormley N, Kazandjian D, et al. FDA Analysis of racial demographics in multiple myeloma trials. Blood. 2017;130(Supplement 1):4352-4352.
Disclaimer: The content of Letters to the Editor is the opinion of the author and does not represent the official position of the American Society of Hematology unless so stated.
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