# Long-Term Survival with Daratumumab, Lenalidomide and Dexamethasone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma Patients—A Survey from Two Italian Centers

**Authors:** Vittorio Del Fabro, Lara Gullo, Giuliana Giunta, Giuseppina Uccello, Claudia Bellofiore, Cristina Lo Faro, Dario Leotta, Federica Elia, Veronica Vecchio, Chiara Sorbello, Ugo Consoli, Alessandra Romano, Francesco Di Raimondo, Manlio Fazio, Fabio Stagno, Concetta Conticello

PMC · DOI: 10.3390/diseases14020081 · 2026-02-21

## TL;DR

This study shows that the D-Rd treatment combination leads to long-term survival in transplant-ineligible multiple myeloma patients.

## Contribution

The study confirms the effectiveness of D-Rd as a first-line therapy for transplant-ineligible patients.

## Key findings

- 90% of patients achieved at least a partial response with D-Rd treatment.
- 59% of patients achieved a very good partial response or better.
- Higher beta-2-microglobulin levels correlated with lower treatment response.

## Abstract

Background: Multiple myeloma (MM) is a clonal plasma cell neoplasm representing the second most common hematological malignancy. The combination of daratumumab, lenalidomide and dexamethasone (D-Rd) was first approved by the EMA (European Medicines Agency) for the treatment of relapsed/refractory multiple myeloma (RRMM) patients, and was subsequently approved for first-line therapy, based on the results of POLLUX and MAIA trials, respectively. Methods: In this survey, we retrospectively collected data from 96 consecutive transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) patients treated with the D-Rd combination. Results: The median age was 73 years; the median progression free survival (mPFS) and median overall survival (mOS) were not reached (NR); the overall response rate (ORR), defined as patients who obtained at least a partial response (PR), was 90%; 59% of patients achieved a very good partial response (VGPR) or better. A strong negative correlation was observed between treatment response and elevated beta-2-microglobulin levels. Conclusions: This study confirms the efficacy of the D-Rd combination as first-line therapy for TIE-NDMM patients, suggesting that achieving at least a PR—and particularly a VGPR—may represent a strong predictor of long-term remission and survival, even in the era of new combinations based on the use of quadruplets.

## Linked entities

- **Chemicals:** lenalidomide (PubChem CID 216326), dexamethasone (PubChem CID 5743)
- **Diseases:** multiple myeloma (MONDO:0009693)

## Full-text entities

- **Genes:** CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, HLA-G (major histocompatibility complex, class I, G) [NCBI Gene 3135] {aka MHC-G}
- **Diseases:** death (MESH:D003643), Neutropenia (MESH:D009503), EMD (MESH:D023981), cytopenias (MESH:D006402), mOS (MESH:D011475), plasma cell neoplasm (MESH:D054219), injury to (MESH:D014947), Anemia (MESH:D000740), toxicity (MESH:D064420), TIE (MESH:D000072676), bone lesions (MESH:D001847), Extra-Medullary Disease (MESH:D018276), para-osseous or extramedullary disease (MESH:D010001), Infections (MESH:D007239), MM (MESH:D009101), Stable (MESH:D060050), SD (MESH:D012735), Gastrointestinal toxicity (MESH:D005767), SARS-CoV-2 infection (MESH:D000086382), pneumonia (MESH:D011014), Diarrhea (MESH:D003967), renal impairment (MESH:D007674), organ dysfunction (MESH:D009102), Frail (MESH:D000073496), infectious complications (MESH:D003141), ISS (MESH:D062706), hematologic malignancy (MESH:D019337)
- **Chemicals:** D-VMP (-), melphalan (MESH:D008558), Isatuximab (MESH:C000599209), FDG (MESH:D019788), Dexamethasone (MESH:D003907), Lenalidomide (MESH:D000077269), Bortezomib (MESH:D000069286), trimethoprim-sulfamethoxazole (MESH:D015662), aspirin (MESH:D001241), prednisone (MESH:D011241), Daratumumab (MESH:C556306), low-molecular-weight heparin (MESH:D006495), acyclovir (MESH:D000212)
- **Species:** Homo sapiens (human, species) [taxon 9606], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939896/full.md

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Source: https://tomesphere.com/paper/PMC12939896