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P899: REAL-WORLD ASSESSMENT OF TREATMENT PATTERNS AND OUTCOMES IN PATIENTS WITH LENALIDOMIDE-REFRACTORY RELAPSED/REFRACTORY MULTIPLE MYELOMA FROM THE OPTUM DATABASE
Open accessAbstract
Background: New treatment combinations using proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies have significantly improved survival outcomes in patients with multiple myeloma (MM). However, for patients who relapse and/or become refractory after exposure to PIs and IMiDs, selecting the next regimen remains a challenge. There are limited data characterizing treatments and outcomes in this difficult-to-treat population. Aims: To characterize treatment patterns and outcomes in difficult-to-treat patients with MM, stratified by their number of prior lines of therapy (PL). Methods: Data were derived from the Optum deidentified US claims and electronic health record (EHR) database. Patients with MM (index diagnosis in or after Jan 2011) were selected if they received 1-3 PL, including with a PI and an IMiD, and were refractory to lenalidomide. Subsequent treatments beginning in or after Jan 2016 were included to focus on contemporary therapies. Time zero (T0) was the date when the first subsequent therapy started after patient met inclusion criteria. Patient characteristics were assessed at T0. Time-to-event analyses were estimated using the Kaplan-Meier method (starting at T0) for overall survival (OS) and time to next treatment (TTNT). The log-rank test for trend was applied to compare Kaplan-Meier curves for OS by line of therapy. Results: The database included a total of 13,615 (claims) and 22,626 (EHR) patients with an index diagnosis of MM and ≥1 line of therapy. 1,028 (claims) and 1,416 (EHR) patients met inclusion criteria. Median age was 72 (claims) and 68 (EHR) years; 53.4% (claims) and 52.1% (EHR) were male. 12.2% (claims) and 4.9% (EHR) of patients received stem cell transplant prior to T0. Patients in both cohorts had significant comorbidities with mean Charlson Comorbidity Index 3.9 (claims) and 3.2 (EHR). Hypertension and renal failure were among the most prominent comorbidities. The most common subsequent treatment regimens based on hierarchy were daratumumab (22.1% claims; 17.4% EHR), carfilzomib (10.6% claims; 18.4% EHR), and pomalidomide based (12.3% claims; 8.7% EHR). Daratumumab/pomalidomide/dexamethasone was the most frequently used regimen (5.4% claims; 3.8% EHR). For claims data, median OS (months) was 36.7 (95% CI: 31.7-41.2). Median OS was not reached (42.3-NE) for patients with 1 PL (n=546), was 26.2 (21.7-35.7) for patients with 2 PL (n=380) and was 12.1 (7.6-25.0) for patients with 3 PL (n=102). Median TTNT (months) was 5.3 (4.9-5.9) overall, including 4.6 (4.3-5.1) for patients with 1 PL, 6.4 (5.3-7.6) for patients with 2 PL, and 6.0 (4.9-9.4) for patients with 3 PL. For EHR data, median OS was 34.0 (28.2-42.8), with median OS of 46.9 (42.8-NE) for patients with 1 PL (n=587), 28.2 (23.8-41.7) for patients with 2 PL (n=584), and 20.8 (14.9-29.8) for patients with 3 PL (n=245). Median TTNT was 5.8 (5.1-6.5) overall, with values of 5.1 (4.7-6.5) for patients with 1 PL, 6.2 (5.3-7.6) for patients with 2 PL, and 5.8 (4.4-8.2) for patients with 3 PL. Image:Summary/Conclusion: PI-exposed, lenalidomide-refractory patients with 1-3 PL were treated with various regimens. These patients have poor OS and progress quickly through current therapies, suggesting poor progression-free survival. OS is reduced with each successive line of therapy. This analysis highlights the need for new effective regimens for this patient population.
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Treating relapsed/refractory multiple myeloma is increasingly challenging as the evolving frontline landscape complicates second-line treatment selection.
“Treating relapsed/refractory MM (RRMM) is increasingly challenging1,2 as the evolving frontline landscape complicates second-line treatment selection.”
From Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma (2026) · cites this paper as [1]
The Background says selecting the next regimen remains challenging for patients who relapse or become refractory after exposure to proteasome inhibitors and immunomodulatory drugs. It does not establish that treatment is becoming increasingly challenging across RRMM generally. (LLM, conf=0.82)
Experimental — accuracy not yet measuredMost patients with multiple myeloma have a relapse after standard treatment, and outcomes worsen with each subsequent line of therapy.
“outcomes worsen with each subsequent line of therapy. 3-5”
From Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. (2023) · cites this paper as [5]
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Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma.
San-Miguel, J., Dhakal, B., Yong, K., Spencer, A., Anguille, S., Mateos, M.-V., Fernández de Larrea, C., Martínez-López, J., Moreau, P., Touzeau, C., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2303379 · Cited by 827
Self-citationTeclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma
Costa, L. J., Bahlis, N. J., Perrot, A., Nooka, A. K., Lu, J., Pawlyn, C., Mina, R., Caeiro, G., Kentos, A., Hungria, V., et al. (2026) · New England Journal of Medicine · doi:10.1056/nejmoa2514663 · Cited by 119
Raab, M. S., Zamagni, E., Manier, S., Rodríguez‐Otero, P., Schjesvold, F. H., & Broijl, A. (2023) · eJHaem · doi:10.1002/jha2.743 · Cited by 17
Hartley-Brown, M. A., Weisel, K. C., Bitetti, J., Carter, J. A., McNamara, S., Purser, M. F., Palumbo, A., & Richardson, P. G. G. (2024) · British Journal of Haematology · doi:10.1111/bjh.19627 · Cited by 17
“66,67 In the 8 studies reporting ORR (Figure 4C), ORR varied between 14.0% ( n = not recorded) 68 and 90.1% ( n = 33).”
InfluentialCilta-cel, a BCMA-targeting CAR-T therapy for patients with multiple myeloma
Jagannath, S., Jackson, C. C., Schecter, J. M., Lendvai, N. K., Sun, H., Akram, M., Patel, N., & Martin, T. G. (2024) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2024.2352591 · Cited by 13
“Despite the availability of these regimens over the past few years, recent analyses of the early-line lenalidomide-refractory population showed poor patient outcomes and a lack of consistent treatment approaches in real-world (RW) settings [37–40].”
BackgroundSelf-citationTouzeau, C., Lipe, B., Khan, A., Dhakal, B., Nair, S., He, J.-M., Mendes, J., Lee, S. P., Lonardi, C., Slaughter, A. R., et al. (2025) · Advances in Therapy · doi:10.1007/s12325-025-03308-2 · Cited by 2
Self-citationDhakal, B. (2024) · The Hematologist · doi:10.1182/hem.v21.3.202432 · Cited by 1
Self-citationChng, W. J., Wu, D. B., Wu, C., Springford, A., Daly, C., & Jung, S. (2025) · Clinical Lymphoma Myeloma & Leukemia · doi:10.1016/j.clml.2025.02.007 · Cited by 1
Costa, L. J., Nair, S., O’Hara, M., Slavcev, M., Gupta‐Werner, N., Doyle, M., Ammann, E. M., Patel, S., Lin, X., & Mateos, M. (2026) · Clinical Lymphoma Myeloma & Leukemia · doi:10.1016/j.clml.2026.04.009
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Metadata
- Authors
- Dhakal, B., Einsele, H., Potluri, R., Schecter, J., Deraedt, W., Lendvai, N., Slaughter, A., Lonardi, C., Nair, S., He, J., Joseph, N., Cost, P., Valluri, S., Yalniz, F., Pacaud, L., & Yong, K.
- Affiliations
- Medical College of Wisconsin (US)
- Universitätsklinikum Würzburg (DE)
- SmartAnalyst Inc, New York
- Janssen Research & Development (United States) (US)
- Janssen (Belgium) (BE)
- Cilag (Switzerland) (CH)
- Janssen, Buenos Aires, Argentina
- Janssen Global Services, LLC, Raritan
- Janssen Scientific Affairs (United States) (US)
- Legend Biotech (United States) (US)
- University College London (GB)
- Corresponding author
- Dhakal, B.
- Venue
- HemaSphere
- Publisher
- Wiley
- Published
- 2022-06
- Volume
- 6
- Pages
- 790-791
- ISSN
- 2572-9241 (ISSN-L)
- PMC
- PMC9430637
- OpenAlex
- W4283322059
- Cited by
- 9
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 2
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- HemaSphere (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- relapsed/refractory multiple myeloma, lenalidomide-refractory disease, treatment patterns, overall survival, time to next treatment, anti-CD38 monoclonal antibody, proteasome inhibitors, immunomodulators, prior lines of therapy, real-world outcomes, comorbidities, stem cell transplantation
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