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5153 Pomalidomide, Bortezomib and Dexamethasone in Multiple Myeloma Patients Double Refractory to Lenalidomide and Anti-CD38 Monoclonal Antibodies: A Multicentric Italian Retrospective Study

Program: Oral and Poster Abstracts
Session: 907. Outcomes Research: Plasma Cell Disorders: Poster III
Hematology Disease Topics & Pathways:
Research, Combination therapy, Adult, Clinical Research, Plasma Cell Disorders, Diseases, Therapy sequence, Real-world evidence, Treatment Considerations, Lymphoid Malignancies, Study Population, Human
Monday, December 9, 2024, 6:00 PM-8:00 PM

Carmine Liberatore1*, Paola Tacchetti, MD, PhD2*, Concetta Conticello, MD3*, Gregorio Barila4*, Elisabetta Antonioli5*, Angelo Belotti, MD6*, Anna Maria Cafro, MD7*, Laura Paris, MD8*, Velia Bongarzoni9*, Massimo Gentile, MD10*, Matteo DA VIA, MD11*, Barbara Gamberi, MD12*, Sara Pezzatti13*, Fabrizio Ciambelli, MD14*, Mariagrazia Garzia15*, Ombretta Annibali, MD16*, Francesca Fazio17*, Giusy Antolino18*, Nicola Sgherza19*, Francesca Farina20*, Annalisa Citro21*, Monica Galli22*, Vittorio Del Fabro23*, Claudio Salvatore Cartia, MD24*, Francesca Fioritoni25*, Katia Mancuso, MD, PhD2,26*, Irene Attucci27*, Maria Luisa Pioltelli28*, Michele Puppi, MD29*, Sofia Terlizzi30*, Chiara Lisi31*, Virginia Valeria Ferretti32*, Massimo Offidani, MD 33*, Maria Teresa Petrucci, MD31* and Silvia Mangiacavalli, MD24*

1Hematology Unit, Department of Oncology and Hematology,, Ospedale Santo Spirito, Pescara, ITA
2Istituto di Ematologia “Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
3AOU Policlinico G. Rodolico-San Marco, University School of Medicine, Catania, Italy, Catania, ITA
4Hematology Unit, Ospedale San Bortolo, Vicenza, Italy
5Careggi Hospital and University of Florence, Firenze, Italy
6Department of Hematology, ASST Spedali Civili di Brescia, Brescia, Italy
7Department of Hematology, GOM Niguarda Hospital, Milan, Milan, ITA
8Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
9Department of Hematology, San Giovanni-Addolorata Hospital, ROMA, ITA
10Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy, Cosenza, Italy
11Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
12Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, Italy
13Department of Hematology and Transplantation, Azienda Socio Sanitaria Territoriale di Monza ASST-Monza, St Gerardo Hospital, Monza, Italy
14SC Ematologia, ASST Valle Olona - Ospedale di Circolo, Busto Arsizio, Italy
15Azienda Ospedaliera San Camillo Forlanini, UOC Hematology and stem cell transplant, Roma, ITA
16Division of Hematology, Stem Cell Transplantation,, Fondazione Policlinico Universitario Campus Bio Medico, Roma, Italy
17Division of Hematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University of Rome, ROMA, Italy
18Multiple Myeloma GIMEMA Lazio Group, rome, ITA
19Department of Precision and Regenerative Medicine and Ionian Area, "Aldo Moro" University School of Medicine, Bari, Italy
20Hematology and BMT unit, IRCCS Ospedale San Raffaele, Milano, Italy
21UOC Ematologia, Ospedale Civile di Legnano, Legnano, Italy
22Hematology and Bone Marrow Transplant Unit, Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
23Division of Hematology, Azienda Policlinico-S. Marco, University of Catania, Catania, ITA
24Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
25Department of Haematology, Pescara, ITA
26Department of Medical and Surgical Science, DIMEC, University of Bologna, Bologna, ITA
27Careggi University Hospital, florence, Italy
28Department of Hematology, GOM Niguarda Hospital, Milan, ITA
29Istituto di Ematologia "Seràgnoli", IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
30Department of Hematology, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy
31Division of Hematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University of Rome, Roma, Italy
32Unit of Biostatistics and Clinical Trial Center, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy
33Clinica di Ematologia Ospedali Riuniti Ancona, Ancona, Italy

Background: Drug refractoriness negatively impacts outcome of relapsing multiple myeloma (MM) patients (pts). Increased use of continuous Lenalidomide (Len) and anti-CD38 Monoclonal Antibodies (MoAb) since the 1° line, will increase rates of pts double refractory (DR) to anti-CD38 MoAb+Len after 1 or 2 lines of therapy (LoT).For these pts, especially those with early progression (<12 months) from therapy initiation, salvage treatments available in daily practice - like PVD (pomalidomide, bortezomib, dexamethasone) - are limited. Furthermore most clinical trial leading to their approval did not include anti-CD38 MoAb+Len DR pts. In the OPTIMISMM study, Len-refractory pts treated with PVD had a median PFS of 9.5 months, with longer PFS in Len-refractory pts treated after 1 LoT (17.8 months). None of the pts enrolled in the OPTIMISMM trial were previously exposed to anti-CD38 MoAb, thus data on PVD outcomes in MoAb+Len DR MM pts are limited.

Aims: To explore the real-life outcome of PVD in a population of MM pts DR to IMIDs and anti-CD38 MoAbs after 1 or 2 LoT.

Methods: We retrospectively reviewed data of 74 MM pts DR to MoAb+Len after 1 or 2 LoT, consecutively treated with PVD regimen according to on-label schedule across 20 Italian centers. The study received ethics committee approval, all pts provided informed consent. Categorical variables were described as counts and percentage, quantitative ones as median and interquartile range (IQR). OS and PFS were estimated by Kaplan-Meier method. Pts were considered responsive if achieving ≥ partial remission (PR) according to IMWG criteria. To evaluate the effect of best response on disease progression, PFS was defined as the time between date of best response and progression or death. The effect of predictors on PFS was evaluated by Cox regression model. All statistical analyses were performed using Stata 18

Results: Characteristics of the cohort of pts at time of PVD starting were: median age 74 years (IQR: 66-76), isotype distribution was 58% IgG, 27% IgA, and 15% light chain, ISS and R-ISS stages I/II/III were distributed as follows 13.8%/31%/55.2% and 5.5%/48.6%/45.9%. FISH data, collected before starting PVD, were available for 42 pts (57%), with 31 pts (42%) having high-risk abnormalities such as t(4;14), t(14;16), del(17p) and gain/ampl(1q21). Nine pts (12,2%) had extramedullary disease. PVD was started for symptomatic relapse in 77% (57 pts), while in 23% (17 pts) for biochemical relapse. All pts were MoAb+Len DR when starting PVD: 56 pts (75,6%) became MoAb+Len DR after receiving Daratumumab-Lena-Dexamethasone (DRd) as 1° LoT until progression, whereas 18 patients (24%) became MoAb+Len DR after receiving DRd in 2° LoT following bortezomib-based 1° LoT (10 pts after VTD followed by transplant without maintenance, and 8 pts after VMP). Median time from diagnosis to PVD starting was 21 months (IQR: 11-34 months), 36 pts (48.6%) were in early progression in course of DRd (<12 months from DRd starting). After a median follow up of 5.7 months (IQR: 3.6-12.8), median number of PVD cycles was 6 (IQR: 4-10). The median time to best response was 2.9 months (IQR: 1.8-4.5 months). The overall response rate was 75% (CR 20%, VGPR 27%, PR 28%). The median PFS after PVD initiation was 8 months (95%CI: 5.7-10.8 months) for the whole cohort and 7 months (95%CI: 5.3-10.8 months) for pts DR after 1 LoT. Univariate analysis found no significant association between PFS and time from diagnosis to PVD initiation or the number of LoT before acquiring DR status (1 vs 2)(all p-values > 0,7). There is a positive association between response to PVD and outcome (p=0.021), with longer PFS in pts with ≥VGPR vs <VGPR (HR= 3.1; 95%CI: 1.3-6.9; p=0.008). Toxicity profile was consistent with OPTISMM data. Median OS was 17.8 months (95%CI: 12.2-not reached).

Conclusions: To our knowledge, this is the first study exploring the outcome of PVD regimen in a real-life population of MM pts becoming double refractory to IMIDs and anti-CD38 MoAb after 1 or 2 LoT. In this setting, PVD proved safe and achieved a significant response rate. Nonetheless, the duration of response and survival were limited, highlighting the need for more extensive access to innovative therapies, especially in the setting of double refractory pts with early relapse after exposure to both IMIDS and anti-CD38 MoAb in 1 or 2 LoT.

Disclosures: Belotti: GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Menarini Stemline: Membership on an entity's Board of Directors or advisory committees. Paris: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodation; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodation; Takeda: Honoraria, Other: Travel, accommodation; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodation; Menarini Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees. Petrucci: Menarini: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSF: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jansen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mangiacavalli: Takeda: Honoraria; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; IRCCS Fondazione Policlinico San Matteo, Pavia: Current Employment; Menarini Stem Line: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria.

*signifies non-member of ASH