Introduction

Despite the tremendous improvement in the treatment landscape of multiple myeloma (MM) patients, autologous hematopoietic cell transplantation (AHCT) remains the standard of care in the first line of treatment for young patients eligible for AHCT. Quadruplets have been introduced as the mainstay of induction treatment. This study evaluates the long-term efficacy and outcomes of AHCT in a real-world cohort of MM patients receiving either daratumumab-based quadruplets or bortezomib-based triplets as induction therapy.

Methods

We retrospectively analyzed 84 consecutive patients with multiple myeloma (MM) who underwent autologous hematopoietic cell transplantation (AHCT) at our center between 2019 and 2025.

Results

The median age at diagnosis was 56 years (range: 31–71), with a male-to-female ratio of 48:36. Myeloma subtypes included IgG (n=40), IgA (n=21), IgD (n=1), serum free light chain-only (sFLC, n=20), solitary plasmacytoma (n=1), and solitary plasmacytoma with minimal marrow involvement (n=1). At diagnosis, ISS stage Ι/ΙΙ/ΙΙΙ was observed in 24,18 and 18 patients and Revised ISS (R-ISS) stage I/II/III in 25, 26, and 10 patients, respectively; plasmacytomas were present in 25 patients, with 10 classified as extraosseous. Cytogenetic analysis was available in 75 patients. Forty-nine patients had normal karyotype, 8 hyperdiploid, 4 hypodiploid. Regarding FISH aberrations, deletion 17p was detected in 5, deletion 1p or addition 1q in 20, translocation t(11;14) in 8, t(4;14) in 9, and t(14;16) in 1 patient respectively. High-risk cytogenetic abnormalities were identified in 30 patients. High-risk disease features—defined by ISS/R-ISS stage III, presence of high-risk cytogenetics, or plasmacytoma—were present in 65% of Group A and 57% of Group B. Among the cohort, 49 patients received daratumumab-based quadruplet induction therapy (Group A), while 35 were treated with bortezomib-based triplets (Group B). Disease status at the time of transplantation showed complete response (CR) in 22 patients (49%) in Group A and 10 patients (28%) in Group B. Stem cell mobilization yielded a median of 3.42×10⁶ CD34⁺ cells/kg (range: 2.00–9.5) vs 4.11×10⁶ cells/kg (range: 2.00–9.3) and plerixafor was required in 59% vs 46% in Groups A and B and respectively .Median time to neutrophil and platelet engraftment was similar to both treatment groups [11 days in both groups for neutrophil (range: 9–13 and 7–13), and 13 days (range: 10–26) vs 11 days (range: 8–23) for platelet in Groups A and B . The median follow-up duration was 29 months for Group A and 65 months for Group B. Overall 2-year sustained CR was 77.1% . Daratumumab-based quadruplet induction was associated with a significantly lower 2-year cumulative incidence of relapse compared to triplets (12.8% vs 28.6%, Gray's p = 0.026) and a reduced cause-specific hazard of relapse (HR = 0.42, 95% CI: 0.21–0.84, p = 0.014). Median TTP was 23.8 months in Group A and 17.6 months in Group B (p < 0.05). For the full cohort, high-risk patients had a median TTP of 31.8 months (95% CI: 27.3–36.2) compared to 38.1 months (95% CI: 23.8–52.4) in standard-risk patients (p = 0.039). Although pre-transplant measurable residual disease (MRD) did not predict TTP, patients who achieved sustained MRD negativity (10⁻⁵ sensitivity for ≥1 year post-AHCT) experienced longer TTP (36.7 vs 32.8 months, p = 0.0014).

Conclusion

Autologous stem cell transplantation remains an effective treatment option for multiple myeloma, even in the era of novel induction regimens. Daratumumab-based quadruplets do not compromise stem cell mobilization and are associated with high rates of sustained MRD negativity—supporting their use as optimal induction therapy in eligible patients.

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2025
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