-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1871 Improved Overall Survival Among Luspatercept Responders and Predictors of Response

Program: Oral and Poster Abstracts
Session: 637. Myelodysplastic Syndromes – Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
adult, Research, MDS, Clinical Practice (Health Services and Quality), elderly, Non-Biological therapies, Clinical Research, health outcomes research, Chronic Myeloid Malignancies, Diseases, patient-reported outcomes, real-world evidence, Therapies, Myeloid Malignancies, survivorship, Study Population, Human
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Angela Consagra1*, Luca Lanino, MD2, Najla H Al Ali, MS3*, Luis E. Aguirre, MD4, Zhuoer Xie, MD, MS5, Onyee Chan, MD3*, Gloria Andreossi6*, Luca Rigodanza6*, Alessandro Sanna, MD7*, Marco Gabriele Raddi, MD8*, Alison R. Walker, MD, MPH, MBA9, Andrew T. Kuykendall, MD3, Jeffrey Lancet, MD3, Eric Padron, MD3,10, David A Sallman, MD3,11, Francesco Restuccia, MD12*, Alessandra Perego13*, Marta Ubezio, MD14*, Bruno Fattizzo, MD15, Marta Riva, MD16*, Alessia Campagna14*, Matteo Giovanni Della Porta, MD14*, Valeria Santini, MD17* and Rami S. Komrokji, MD3

1MDS Unit, DMSC, AOU Careggi, University of Florence, Firenze, Italy
2Humanitas Clinical and Research Center, IRCCS, Rozzano, Milano, Italy
3Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL
4Dana-Farber Cancer Institute, Boston, MA
5H. Lee Moffitt Cancer Institute, Tampa, FL
6MDS UNIT, DMSC, Azienda Ospedaliero-Universitaria Careggi & University of Florence, Florence Italy, Florence, Italy
7Hematology, AOU Careggi, Florence, Italy
8Careggi Hospital, Florence, Italy
9H.Lee Moffitt Cancer Center & Research Institute, Tampa, FL
10Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL
11H. Lee Moffitt Cancer Center, Tampa, FL
12Presidio Ospedaliero, Pescara, Italy, Pescara, Italy
13Ospedale San Gerardo, ASST, Monza, Italy, Monza, ITA
14Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy
15Department of Oncology and Onco-hematology, FONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO, Milano, Italy
16Department of Hematology, ASST Grande Ospedale Metropolitano Niguarda Cancer Center, Milano, Italy
17MDS UNIT, DMSC, Azienda Ospedaliero-Universitaria Careggi & University of Florence, Florence, Italy


Luspatercept (luspa) is a first-in-class erythroid-maturation agent approved for red blood cells transfusion dependent (RBC-TD) lower risk myelodysplastic syndrome (LR-MDS) with ring sideroblast (RS) based on MEDALIST clinical trial.

We aimed to explore impact of luspa on overall survival (OS) and predictors of response in a large cohort of pts treated with luspa, collected from Moffitt Cancer Center (MCC) and from Fondazione Italiana Sindromi Mielodisplastiche (FISiM).


We evaluated all pts with LR-MDS-RS treated with luspa from MCC cohort since FDA approval, and from a multicenter observational trial of FISiM for pts treated on a compassionate use program. Baseline RBC transfusion burden (TB) was defined as: non-transfusion dependent (NTD) (0 units in 8 weeks prior luspa), low TB (LTB) (1-5 units/8 weeks) and high TB (HTB) (≥ 6 units/8 weeks). A hematological response (HI) was defined as an (i) objective Hgb increase of > 1.5 g/dl in NTD, and (ii) RBC-TI with Hgb increase of 1.5 g/dl, or RBC-TI without Hgb 1.5 g/dl increase, or >50% reduction in RBC TB among RBC-TD. Somatic mutation (MT) data were available for 137 pts.


Between January 2020 and March 2023, 331 pts were treated with Luspa (Table-1). The median age was 69 years; 308 pts (93%) had MDS-RS, 86,1% were intermediate, low or very low risk MDS by R-IPSS and 82% (105/128) were moderate low (ML), low (L) or very low (VL) by IPPS-M. SF3B1 MT was detected in 86.3% (120/139) with a median VAF of 37.7. The mean Hgb level was 7.97 g/dl and 93.7% were RBC-TD. Majority had prior erythroid stimulating agents (ESA) (93.6%). In the MCC cohort 42.9% (52/121) had prior hypomethylating agents (HMA) therapy, and 31.4% (38/121) had prior lenalidomide (len).

With a median follow up of 14.6 mos from starting luspa treatment, the median OS was not reached (NR) among responders to luspa compared to 24.5 mos for non-responders (p <.001) (Figure-1). The median OS benefit was more pronounced among pts with RBC-TI and Hgb> 1.5 g/dl increase compared to other categories of response. In the NTD group at baseline, the median OS among luspa responders was NR compared to 22.7 mos among non-responders (P< .001). In the LTB group at baseline median OS was NR as well among luspa responders compared to 29.9 mos in non-responders (p=.002) and finally among HTB group at baseline, the median OS among luspa responders was 35.4 mos compared to 21.2 mos in non-responders (p=.007). In multivariable analysis adjusting for IPSS-M and baseline RBC-TD, response to luspa was independently associated with improved OS, HR .39 (95% CI .18-.83), p= .015

The overall HI rate to luspa was 40.6% (134/330) (Table-1), 85% of pts needed dose escalation, HI correlated with baseline RBC-TB where 80% (16/20) NTD, 60.2% (65/108) LTB and 41.8% HTB (77/184) achieved HI respectively, p< .001. By IPSS-M, there was a trend for lower HI with higher risk disease (100% in VL, 60.3% in L, 36.7% in ML, 56.3% in MH, 16.7% in H risk pts, p=.051). There was a mild trend for higher response among SF3B1 MT pts compared to wild type, 54% (64/119) versus 42% (8/19), p=.34. The segregation of SF3B1 MT cases into three independent groups based on IPSS-M, showed that HI rate was better in SF3B1β (SF3B1 and any gene from BCOR, BCORL1, NRAS, RUNX1, SRSF2, or STAG2) and SF3B1α (as any other mutant) than SF3B15q (concomitant presence with isolated del5q): 50% (7/14), 58.8% (57/97), and 0% (0/5) respectively, p=.03. Among SF3B15q pts, 4 had been treated with len before luspa and only 1 had achieved an HI with prior len.

Among pts with SF3B1 MT, we observed a trend for higher response in pts with the hotspot K700E, 62.7% (37/59) vs 47.4% (27/57) in non-K700E, p=.097. In pts with SF3B1 MT, divided by median VAF, we observed a trend for better HI with VAF was >38, 63.5% (33/52) vs 45.3% (24/53), p=.062.

Among responders, the median duration of response was 14.1 mos. As of last follow up, 85% pts (191/224) discontinued treatment. Reason of discontinuation was lack of response in 126 pts, loss of response in 26 patients and adverse events in 6 pts. The most common reported adverse events were fatigue (n=10), GI symptoms (n=4), shortness of breath and arthralgia (1 each).


Our RWD in the largest luspa treated cohort demonstrates OS benefit to luspa response. Low baseline RBC-TB dependency, lower risk IPSS-M, SF3B1 MT, SF3B1-K700E mutation and SF3B1α co-mutations correlated with higher response rates. Our data emphasizes the impact of RBC-TI in LR-MDS.

Disclosures: Xie: Moffitt Cancer Center: Current Employment; Novartis: Speakers Bureau. Sanna: Astrazeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau. Kuykendall: Novartis: Consultancy; CTI: Consultancy; Blueprint: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; AbbVie: Consultancy; Incyte: Consultancy; Imago: Consultancy; GSK: Consultancy; Sierra Oncology: Research Funding; Protagonist Therapeutics, Inc.: Consultancy, Research Funding; Prelude: Research Funding. Lancet: Globe Life Sciences: Consultancy; Celgene: Consultancy, Research Funding; Boxer Capital: Consultancy; BerGenBio / DAVA Oncology: Consultancy; Atheneum: Consultancy; AbbVie Inc.: Consultancy; Jasper Therapeutics: Consultancy; Jazz: Consultancy; MD Anderson: Consultancy; MEDTalks: Consultancy; Novartis: Consultancy; Peer Voice: Consultancy; Servier: Consultancy; Tegus: Consultancy; The Dedham Group: Consultancy. Padron: Pharmaessentia: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; CTI: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Gillead: Membership on an entity's Board of Directors or advisory committees. Sallman: Aprea, Jazz: Research Funding; AbbVie, Affimed Gmbh, Gilead, Incyte, Intellisphere, LLC, Molecular Partners AG, PGEN Therapeutics, Inc., Takeda, Zentalis; Advisory board for AvenCell, BlueBird Bio, BMS, Intellia, Jasper Therapeutics, Kite, Magenta Therapeutics, NKARTA, Novartis, Orbita: Consultancy. Fattizzo: Agios: Consultancy, Research Funding, Speakers Bureau; Janssen: Speakers Bureau; Zenas Biopharma: Research Funding; Sobi: Speakers Bureau. Della Porta: Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Santini: BMS/Celgene: Other: Advisory boards; Servier: Other: Advisory boards; Syros: Other: Advisory boards; Novartis: Other: Advisory boards; Gilead: Other: Advisory boards; Otsuka: Other: Advisory boards; Geron: Other: Advisory boards; CTI: Other: Advisory boards; Janssen: Other: travel grant; AbbVie: Other: Advisory boards. Komrokji: BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy; AbbVie, CTI biopharma, Jazz, Pharma Essentia, Servio: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Rigel, Taiho, DSI: Honoraria, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH