Introduction: LEN has long been a foundational therapy in MM. Since the European approval of daratumumab and isatuximab, these anti-CD38 mAbs have become increasingly central to MM treatment. Initially indicated for relapsed/refractory MM (RRMM), anti-CD38 mAbs are increasingly being used in newly diagnosed MM (NDMM), for both transplant-eligible and -ineligible patients, driven by recent clinical trials evaluating their role in quadruplet regimens. This study aimed to describe and assess outcomes of the evolving population of patients with MM in Germany with prior exposure to LEN and anti-CD38 mAbs using real-world data.

Methods: A retrospective, multicenter, survey-based cohort study was conducted across Germany as part of the TherapyMonitor MM research project, including 9477 patients with NDMM and RRMM treated in 2016–2024. Data were collected quarterly and designed to be representative across regions and institutions. Patient characteristics and LEN and anti-CD38 mAbs utilization in NDMM and RRMM (by line of therapy [LOT] and by calendar year) were assessed. Descriptive statistics were reported for baseline patient characteristics and treatment patterns. Kaplan-Meier curves were created for time to next treatment (TTNT) and overall survival (OS). TTNT was defined as the time from index (initiation of new LOT after anti-CD38 mAbs and LEN exposure) to death, start of a new LOT, or censor date; OS was defined as the time from index to death; both were reported for patients with RRMM with prior exposure to regimens containing LEN and anti-CD38 mAbs (not necessarily within the same LOT).

Results: In the full MM study cohort (2016–2024), 56% (5309/9477) of patients had used anti-CD38 mAbs and 48% (4527/9477) had LEN and anti-CD38 mAbs (at any time). Use of anti-CD38 mAbs in combination with LEN in NDMM increased from 1% in 2019 to 39% (833/2119) in 2024. In the RRMM setting, anti-CD38 mAbs with LEN use in second line (2L) rose from 5% in 2017 to 36% (600/1669) in 2024. In third line (3L), use of anti-CD38 mAbs with LEN was stable up until 2024 at 7% (68/986). In fourth and later lines (4L+), anti-CD38 mAbs with LEN use was ≈3% from 2021 (39/1177) to 2024 (37/1080), a reflection of increasing utilization in earlier lines.

In 2024, 11% of patients in 2L (190/1669) had prior anti-CD38 mAbs exposure, with 8% (132/1669) of patients also exposed to LEN. In 3L, 45% (443/986) had prior anti-CD38 mAbs, and 41% (406/986) had both anti-CD38 mAbs and LEN. In 4L+, 71% (766/1080) had prior anti-CD38 mAbs, 67% (719/1080) also with LEN.

Of patients with prior exposure to both agents in 2L in 2024, 27% were ≤70 years of age (35/132), 80% (105) with ECOG 0–1, 58% (77) had ISS I–II, and 65% (86) were refractory to prior treatment (post hoc assessment per International Myeloma Working Group definition). With subsequent treatment in 3L and 4L+, 73% (297/406) and 64% (449/719), respectively, had ECOG ≤1, 35% (142) and 33% (230) were ≤70 years of age, 46% (186) and 41% (287) had ISS I–II, and 81% (328) and 87% (614) were refractory to ≥1 prior treatment. In 3L, 39% (160) of patients had comorbidities, compared with 53% (377) in 4L+.

The three most common treatments received by patients with RRMM with prior anti-CD38 mAbs and LEN exposure varied slightly by LOT. Isa-Kd (28%), Kd (24%), and DKd (11%) were the most common treatments in 2L; EPd (26%), Isa-Kd (21%), and Kd (11%) in 3L; and Isa-Kd (26%), EPd (19%), and Isa-Pd (17%) in 4L+. Rechallenge with anti-CD38 mAb-containing regimens was also common across 2–4L+: 49% (65/132) in 2L, 33% (135/406) in 3L, and 49% (195/402) in 4L+.

Median TTNT (mTTNT) among patients in 2L+ with prior anti-CD38 mAbs and LEN exposure was 13.8 months (95% CI, 13.0–14.5; N=3373) and the mTTNT decreased with advancing LOTs. In 2L treatment, the mTTNT was 19.2 months (95% CI, 15.8–29.6; N=180); this declined to 14.9 months (95% CI, 14.2–16.4; N=905) in 3L, and further to 12.4 months (95% CI, 12.2–13.1; N=2253) in 4L+. Median OS was not reached at the time of analysis.

Conclusions: Use of anti-CD38 mAbs and LEN in MM has increased substantially in Germany over recent years, resulting in a growing population of patients with prior exposure to both LEN and anti-CD38 mAbs, including those treated in the frontline setting. The TTNT data highlight the opportunity for further therapeutic improvement in this patient population and the need for novel therapeutic modalities to address the evolving treatment landscape.

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2025
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