Real-World Study of Patients with Triple-Class Exposed Relapsed/Refractory Multiple Myeloma: Analysis across a Spectrum of Advanced Disease Stage Medicare Patients in the United States
Authors: Delea Thomas , Moynahan Aaron , Ge Wenzhen , Song Xue , Kroog Glenn S. , Noguera-Troise Irene , Rodriguez Lorenc Karen , Ma Qiufei 
Published: December 2023

Background
Treatment of relapsed/refractory (RR) multiple myeloma (MM) has been transformed by novel therapies including anti-CD38 monoclonal antibodies (mAb), 2 nd and 3 rd generation immunomodulatory drugs (IMiD), and proteasome inhibitors (PI). This has resulted in increasing numbers (no.) of triple-class exposed (TCE) patients (pts), defined as pts who have received an IMiD, ≥1 PI, and ≥1 anti-CD38 mAb. Many TCE pts are exposed to ≥5 drugs in these classes (i.e. penta-exposed [PE]: ≥2 IMID, ≥2 PI, and an anti-CD38 mAb). Some are refractory to ≥1 drug in each class (triple-class refractory [TCR]) and some are both PE and TCR (PE-TCR). Data on real-world outcomes for the spectrum of heavily pre-treated, advanced RRMM pts are limited. This study examined treatment patterns and healthcare resource utilization (HRU) and costs in Medicare-insured pts with TCE RRMM.
Methods
Adult pts with an incident diagnosis (Dx) of MM (≥2 outpatient claims 30-365 days apart OR ≥1 inpatient AND 6 months [mos.] of continuous eligibility prior to first Dx) during the study period (Nov 14, 2006-Dec 31, 2020) who were TCE were selected from the Center for Medicare and Medicaid Services Chronic Conditions Data Warehouse. TCE was defined as having ≥1 claim each for an IMiD, a PI, and an anti-CD38 mAb; PE was defined as having ≥2 claims each for an IMiD and a PI and ≥1 claim for an anti-CD38 mAb (TCE pts were assumed to have RRMM based on exposure). Pts were deemed TCR if refractory to ≥1 regimen each which included a PI, an IMiD, and an anti-CD38 mAb. Pts were considered refractory to a regimen if the period between the last claim or days supplied for any drug in the regimen and the start of the subsequent regimen was &lt;60 days AND none of the drugs in the regimen were present in the next regimen. For each pt, the 1 st line of therapy (LOT) after becoming TCE was considered the index LOT and the date that this LOT initiated was defined as the index date. Pts were followed from the index date until the earliest of end of continuous enrollment or the end of study period. LOTs and treatment regimens were defined using an adaptation of published algorithm developed based on clinical expert opinion (Madduri et al. Future Oncol. 2021). Outcomes included anti-MM treatments received for index LOT, time to discontinuation (TTD), time to next treatment (TTNT), overall survival (OS), and post-index HRU and healthcare costs (adjusted to 2021 USD). Median TTD and OS were obtained by Kaplan-Meier (KM) methods. TTNT was analyzed by cumulative incidence methods with death as a competing risk. HRU and costs (in 2021 USD) were reported on a per patient per month (PPPM) basis.
Results
137,707 pts with an MM Dx during the study period were identified. A total of 2,830 TCE, 1,371 TCR, 1,121 PE, and 774 PE-TCR pts met all other inclusion criteria. Mean age was 76 years in all 4 cohorts, 50-51% were female, 21% (TCR) to 29% (PE) had prior autologous stem cell transplant. The mean no. of prior LOTs ranged from 3.3 (TCE) to 4.5 (PE-TCR). The no. of new TCE pts increased almost 8-fold from 114 in 2016 to 890 in 2020; similar increases were observed for TCR, PE, and PE-TCR pts. Mean (SD) follow-up time (mos.) was 12.4 (10.6) for TCE, 11.9 (10.0) for TCR, 10.9 (10.3) for PE, and 10.1 (9.3) for PE-TCR.
There was no apparent standard of care (SOC) treatment across the 4 cohorts; the most frequently used index LOT regimens were pomalidomide + daratumumab for TCE (17%) and PE (7%), pomalidomide + carfilzomib for TCR (10.3%), and pomalidomide + elotuzumab for PE-TCR (7.4%). In all 4 cohorts, pomalidomide was the most frequently received medication during the index LOT (32.6% [PE-TCR] to 43.3% [TCR]). Median TTD (mos.) ranged from 4.2 (PE-TCR) to 6.9 (TCE). Median TTNT (mos.) ranged from 8.1 (TCR) to 14.6 (TCE). Median OS (mos.) ranged from 13.0 (TCR) to 15.9 (PE). TCE pts had a mean PPPM 0.20 ED visits, 7.02 outpatient visits, 3.73 outpatient pharmacy claims, 0.14 hospitalizations, and 1.18 inpatient days. For TCE pts, mean PPPM total costs were $23,091, the largest share of which was for MM medications ($16,812), followed by other MM-related services ($4,824). Monthly HRU and costs for TCR, PE, and PE-TCR pts were similar to those for TCE.
Conclusions
Despite increasing no. of Medicare-insured TCE, TCR, PE, and PE-TCR MM pts, there is no apparent SOC treatment regimen. With current treatments, TTD, TTNT, and OS are short and HRU and costs are high. These data underscore the high unmet need for new therapies in this growing population.