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Racial differences in clinical trial enrollment, treatment, and survival outcomes in MM

Jan 3, 2021
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Although there are racial variations in the presentation, treatment, and outcomes of many cancers, racial disparities are particularly pronounced in multiple myeloma (MM). Black people are twice as likely as white people to develop monoclonal gammopathy of undetermined significance, the precursor of MM.1 It is also well known that this translates into a two- to three-fold higher incidence of MM, yet studies of mortality and outcomes have been inconclusive.2 It has also been suggested that the representation and reporting of racial minorities in MM trials has been low, which will affect the understanding of the racial disparities seen in the course of MM.3

In a recent systematic review published in Lancet Haematology, Ghulam Rehman Mohyuddin and team commented on the reporting and enrolment of racial minorities in MM randomized controlled trials (RCTs) between 2005 and 2019.3 They identified 100 RCTs that met their inclusion criteria, which included 45,524 patients. The group found that only 26 RCTs reported the racial composition of their enrolled cohorts, and among the 16,452 patients in these trials, 2,612 (16%) were non-white. Only 19 studies reported the number of black patients: 730 (6%) of 12,915 patients. The study assessed the reporting over different periods and found that it had remained stable and that the enrolment of minorities had not changed for the last 15 years (Figure 1). They also found that reporting of race in studies was slightly better in pharmaceutical-led vs academic-led trials (33% vs 18%; p = 0.09). Multinational studies were more likely to recruit minorities than single-country studies (18% vs 13% of patients; p < 0.0001), but the same proportion reported on their study population's racial composition. They conclude that the research community should take steps to rectify the under-representation and reporting of minorities in trials to provide appropriate counseling and equitable care.3

Figure 1. Multiple myeloma clinical trials reporting on race and representation of racial minorities3

A recent publication by Benjamin Derman and colleagues aimed to assess outcomes in a cohort of patients with MM and identify any differences between black and white patients. Their study was published recently in the Blood Cancer Journal.2

Using the Multiple Myeloma Research Foundation (MMRF) CoMMpass registry (NCT01454297), the team included a total of 639 evaluable patients (Table 1). The CoMMpass study collected tissue samples, genetic information, quality of life, and outcomes from patients mainly from the US diagnosed with MM. Cytogenetic changes were inferred from next-generation sequencing CoMMpass data.2

Table 1. Patient characteristics from the MMRF CoMMpass registry2

ASCT, autologous stem cell transplant; ECOG, Eastern Cooperative Oncology Group; IMiD, immunomodulatory drug; PI, proteasome inhibitor.
All values are presented as n (%) unless otherwise stated.
p values were computed using a Chi-square or Fisher's exact test for comparisons of categorical variables and a t-test for continuous variables.

Characteristic

White

(n = 526)

Black

(n = 113)

p value

Age, median (range)

65 (38–89)

63 (34–87)

0.2

Male gender

319 (61)

69 (61)

0.9

Number of high-risk cytogenetic abnormalities

 

 

 

  0

254 (48)

58 (51)

0.6

  1

200 (38)

43 (38)

0.5

  2+

72 (14)

12 (11)

0.4

ECOG performance status

 

 

0.8

  0

164 (35)

34 (34)

 

  1

231 (49)

45 (45)

 

  2

56 (12)

15 (15)

 

  3

21 (4)

6 (6)

 

  4

4 (1)

1 (1)

 

Induction therapy

 

 

0.001

  Any triplet

384 (73)

62 (55)

<0.001

  PI + IMiD triplet

240 (46)

40 (35)

0.05

  Alkylator-based triplet

144 (27)

22 (20)

0.1

  Doublet

118 (22)

46 (41)

<0.001

  Other

24 (5)

5 (4)

1

Received triplet + ASCT

231 (44)

37 (33)

0.04

Received frontline ASCT

260 (49)

44 (39)

0.04

+ Post-ASCT maintenance

157 (60)

26 (59)

0.9

Median age, male gender, high-risk cytogenetic abnormalities, and Eastern Cooperative Oncology Group status were similar across the groups. Black patients were significantly less likely to receive triplet therapies than white patients (55% vs 73%; p < 0.001). Black patients were also less likely to receive frontline autologous stem cell transplant (ASCT; 39% vs 49%; p = 0.04) and combination triplet induction with ASCT (33% vs 44%; p = 0.04).2

In terms of survival outcomes, overall survival (OS) was shorter in black patients compared with white patients (age-adjusted HR, 1.7; 95% CI, 1.2–2.4; p = 0.003), though this was attenuated in patients who received triplet therapy and ASCT. On multivariate analysis, only the lack of frontline ASCT was associated with worse progression-free survival and OS in black patients. Subgroup analysis of those patients who received triplet therapy plus ASCT suggests that the effect on OS is only partially corrected by this combination treatment (age-adjusted HR, 2.3; 95% CI, 0.9–5.8; p = 0.08).2

The team concluded that the reduced OS seen in black patients was not completely overcome by controlling for socioeconomic status surrogate measures, such as access to standard treatment regimens, and that there may be biological or other socioeconomic factors at work in the racial disparities seen in MM outcome.2

A study from England that was published in 2015 in Leukemia and Lymphoma agreed that the incidence of MM was higher in black patients (age-standardized incidence rate, 15.00 per 100,000; 95% CI, 13.50–16.40) than white (6.11 per 100,000; 95% CI. 6.00–6.22), but found that relative survival was better in black patients at 1 (HR, 0.66; 95% CI, 0.55–0.79) and 3 years (HR, 0.69; 95% CI, 0.58–0.83) than white patients. They found similar outcomes in the South Asian group at 1 (HR, 0.65; 95% CI, 0.51–0.82), 3 (HR, 0.72; 95% CI, 0.57–0.90), and 5 years (HR, 0.68; 95% CI, 0.50–0.92). The UK study found a marked increase in ASCT being given to black and Asian patients in 1994–2000 and 2001–2009. The group postulate that, while access to treatments may have been inequitable previously, the more equitable access to treatments seen latterly in England may account for the better outcomes in minority groups. They felt that this could enable the study of biological differences in outcomes, especially with novel therapies.4

  1. Willyard C. How researchers are addressing the racial imbalance in multiple myeloma. Nature. 2020;587(7835):S64-S65. DOI: 10.1038/d41586-020-03228-x

  2. Derman BA, Jasielec J, Langerman SS, et al. Racial differences in treatment and outcomes in multiple myeloma: a multiple myeloma research foundation analysis. Blood Cancer J. 2020;10(8):80. DOI: 10.1038/s41408-020-00347-6

  3. Mohyuddin GR, Koehn K, Costa L, et al. Enrolment of racial minorities across 15 years of multiple myeloma randomised trials; calling on researchers to become agents of change. Lancet Haematol. 2020;7(10):e704-e706. DOI: 10.1016/S2352-3026(20)30281-7

  4. Samy EF, Ross J, Bolton E, et al. Variation in incidence and survival by ethnicity for patients with myeloma in England (2002–2008). Leuk Lymphoma. 2015;56(9):2660-2667. DOI: 10.3109/10428194.2014.1003060

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