Background: Pomalidomide-daratumumab-dexamethasone (DPd) has been shown to be effective in lenalidomide-exposed patients with multiple myeloma (MM). We aimed to evaluate this combination in patients with del(17p), for whom there is no specific treatment. Patients and Methods: The phase II DEDALO study enrolled patients with relapsed/refractory (RR)MM, del(17p), and ≤ 3 previous therapy lines including lenalidomide. Patients received DPd according to the approved schedule. The primary endpoint was minimal residual disease (MRD) negativity (by next-generation sequencing, 10−5 sensitivity). Results: Fifty patients were enrolled, and 45 were eligible. A del(17p) clone size ≥ 55% was observed in 26/45 patients, while TP53 mutations in 10/31. One patient achieved MRD negativity. With a median follow-up of 18.7 months, the median progression-free survival (PFS) was 7.0 months (4.3-13.9) overall, 6.5 in patients with a del(17p) clone size < 55%, 7.6 in those with a clone size ≥ 55%, 3.2 in those with biallelic TP53 alteration, and 11.8 in those with isolated del(17p). Toxicity was consistent with previous studies. Conclusion: This is the first study testing a specific treatment for MM patients with del(17p). We confirmed the severity of this abnormality, particularly in the presence of double TP53 inactivation, and the importance of a thorough biological characterization.
Clinical and Biological Implications of TP53 Abnormalities in Relapsed/Refractory Multiple Myeloma: The DEDALO Study
Patriarca F.;
2026-01-01
Abstract
Background: Pomalidomide-daratumumab-dexamethasone (DPd) has been shown to be effective in lenalidomide-exposed patients with multiple myeloma (MM). We aimed to evaluate this combination in patients with del(17p), for whom there is no specific treatment. Patients and Methods: The phase II DEDALO study enrolled patients with relapsed/refractory (RR)MM, del(17p), and ≤ 3 previous therapy lines including lenalidomide. Patients received DPd according to the approved schedule. The primary endpoint was minimal residual disease (MRD) negativity (by next-generation sequencing, 10−5 sensitivity). Results: Fifty patients were enrolled, and 45 were eligible. A del(17p) clone size ≥ 55% was observed in 26/45 patients, while TP53 mutations in 10/31. One patient achieved MRD negativity. With a median follow-up of 18.7 months, the median progression-free survival (PFS) was 7.0 months (4.3-13.9) overall, 6.5 in patients with a del(17p) clone size < 55%, 7.6 in those with a clone size ≥ 55%, 3.2 in those with biallelic TP53 alteration, and 11.8 in those with isolated del(17p). Toxicity was consistent with previous studies. Conclusion: This is the first study testing a specific treatment for MM patients with del(17p). We confirmed the severity of this abnormality, particularly in the presence of double TP53 inactivation, and the importance of a thorough biological characterization.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
