PMID- 35157306 OWN - NLM STAT- MEDLINE DCOM- 20220406 LR - 20230412 IS - 1097-0142 (Electronic) IS - 0008-543X (Print) IS - 0008-543X (Linking) VI - 128 IP - 8 DP - 2022 Apr 15 TI - Ofatumumab plus HyperCVAD/HD-MA induction leads to high rates of minimal residual disease negativity in patients with newly diagnosed mantle cell lymphoma: Results of a phase 2 study. PG - 1595-1604 LID - 10.1002/cncr.34106 [doi] AB - BACKGROUND: Ofatumumab is a humanized type 1 anti-CD20 monoclonal antibody. Preclinical studies show improved complement-mediated cytotoxicity (CMC) compared to rituximab in mantle cell lymphoma (MCL). This study evaluates the safety and efficacy of combining ofatumumab with HyperCVAD/MA (O-HyperCVAD) in newly diagnosed MCL. METHODS: In this single-arm phase 2 study, 37 patients were treated with the combination of O-HyperCVAD for 4 or 6 cycles, followed by high dose chemotherapy and autologous stem cell transplant. Primary objectives were overall response rate (ORR) and complete response (CR) rate at the end of therapy. Secondary objectives included minimal residual disease (MRD) negativity, progression-free survival (PFS), and overall survival (OS). RESULTS: Median age was 60 years; ORR was 86% and 73% achieved a CR by modified Cheson criteria. The MRD negativity rate was 78% after 2 cycles of therapy, increasing to 96% at the end of induction; median PFS and OS were 45.5 months and 56 months, respectively. Achieving a post-induction CR by both imaging and flow cytometry was associated with improved PFS and OS. Early MRD negativity (post-2 cycles) was also associated with an improved PFS but not OS. There were 3 deaths while on therapy, and grades 3 and 4 adverse events (AEs) were observed in 22% and 68% of the patients. CONCLUSION: The addition of ofatumumab to HyperCVAD/HD-MA led to high rates of MRD negativity by flow cytometry in patients with newly diagnosed MCL. Achieving a CR post-induction by both imaging and flow cytometry is associated with improved overall survival. CI - (c) 2022 American Cancer Society. FAU - Torka, Pallawi AU - Torka P AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Akhtar, Othman S AU - Akhtar OS AUID- ORCID: 0000-0003-1673-9670 AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Reddy, Nishitha M AU - Reddy NM AD - Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Baysal, Bora E AU - Baysal BE AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Kader, Angela AU - Kader A AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Groman, Adrienne AU - Groman A AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Nichols, Jenna AU - Nichols J AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Mavis, Cory AU - Mavis C AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Tario, Joseph D AU - Tario JD AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Block, AnneMarie W AU - Block AW AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Sait, Sheila N J AU - Sait SNJ AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Ghione, Paola AU - Ghione P AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Sundaram, Suchitra AU - Sundaram S AD - Icahn School of Medicine at Mount Sinai, New York, New York. FAU - Przespolewski, Eugene R AU - Przespolewski ER AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Mohr, Alice AU - Mohr A AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Lund, Ian AU - Lund I AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Kostrewa, Jessica AU - Kostrewa J AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - McWhite, Kenneth AU - McWhite K AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - DeMarco, Joseph AU - DeMarco J AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Johnson, Michael AU - Johnson M AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Darrall, Andrea AU - Darrall A AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Thomas-Talley, Rosh-Neke AU - Thomas-Talley RN AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Wallace, Paul K AU - Wallace PK AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Neppalli, Vishala AU - Neppalli V AD - University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Hutson, Alan AU - Hutson A AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. FAU - Hernandez-Ilizaliturri, Francisco J AU - Hernandez-Ilizaliturri FJ AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York. LA - eng SI - ClinicalTrials.gov/NCT01527149 GR - P30 CA016056/CA/NCI NIH HHS/United States GR - Roswell Park Cancer Institute/ GR - National Comprehensive Cancer Network/ PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220214 PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 4F4X42SYQ6 (Rituximab) RN - M95KG522R0 (ofatumumab) SB - IM MH - Adult MH - *Antibodies, Monoclonal, Humanized/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - Humans MH - *Lymphoma, Mantle-Cell/therapy MH - Middle Aged MH - Neoplasm, Residual/diagnosis MH - Rituximab PMC - PMC10086838 MID - NIHMS1882480 OTO - NOTNLM OT - CD20 OT - MIPI score OT - monoclonal antibody OT - p53 OT - survival outcomes EDAT- 2022/02/15 06:00 MHDA- 2022/04/07 06:00 PMCR- 2023/04/11 CRDT- 2022/02/14 12:18 PHST- 2021/11/13 00:00 [revised] PHST- 2021/08/26 00:00 [received] PHST- 2021/12/01 00:00 [accepted] PHST- 2022/02/15 06:00 [pubmed] PHST- 2022/04/07 06:00 [medline] PHST- 2022/02/14 12:18 [entrez] PHST- 2023/04/11 00:00 [pmc-release] AID - 10.1002/cncr.34106 [doi] PST - ppublish SO - Cancer. 2022 Apr 15;128(8):1595-1604. doi: 10.1002/cncr.34106. Epub 2022 Feb 14.