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3034 Phase II Trial of Ibrutinib in Previously Untreated High-Risk Smoldering Mantle Cell Lymphoma

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, adult, Biological therapies, clinical trials, non-Hodgkin lymphoma, Lymphomas, Clinical Research, Diseases, Therapies, Lymphoid Malignancies, Human, Study Population
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Charles Gaulin, MBBS1, Preetesh Jain, MD, MBBS, PhD, DM2, Ranjit Nair, MD1,3, Swami P. Iyer, MD2, Hun Ju Lee, MD1*, Luis Fayad, MD4, Lei Feng, MS5*, Yang Liu, PhD1*, Holly A Hill, MS6*, Yijing Li, BS, MS1*, Chi Young Ok, MD7, Rashmi Kanagal-Shamanna, MD8, Onyeka Oriabure, MSN, RN, NP6*, Wendy Chen, BS, MPAS, MS6*, Asiya Siddiqui, MS2*, Guofan Xu, MBBS, PhD9*, Anita Deswal, MD, MPH, MBBS10*, Cezar Iliescu, MD11*, Maria Badillo12*, Shaoying Li, MD13, Michelle Ky2*, Michelle Avellaneda2*, Guilin Tang, MD, PhD7*, Francisco Vega, MD, PhD14, Christopher R. Flowers, MD, MS1 and Michael L. Wang, MD2

1Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
2Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
3Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Pearland, TX
4Lymphoma/Myeloma, M.D. Anderson Cancer Center, Houston, TX
5Biostatistics, UT MD Anderson Cancer Center, Houston, TX
6Departments of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
7Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
8Department of Hematopathology, The University of Texas M D Anderson Cancer Center, Houston, TX
9Cardiology, University of Texas MD Anderson Cancer Center, Houston, TX
10Geriatrics, MD Anderson Cancer Center, Houston, TX
11Cardiology, The University of Texas MD Anderson Cancer Center, houston, TX
12Lymphoma/ Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
13The University of Texas MD Anderson Cancer Center, Houston, TX
14Department of Hematopathology, MD Anderson Cancer Center , Houston, TX

Background: Mantle cell lymphoma (MCL) patients usually require immediate therapy, however about 20% of newly diagnosed MCL patients can be initially observed. A subgroup of patients who are suitable for initial observation but exhibit high-risk features are of particular concern as they have a propensity to progress. We consider these patients as high-risk smoldering MCL (defined below). Generally, these patients are observed without systemic therapy for 18-24 months. We investigated the impact of single-agent ibrutinib on time to progression for these patients who would otherwise be observed.

Methods: This is a single center, single arm, investigator-initiated phase 2 clinical trial (NCT03282396). High-risk smoldering MCL included one or more of the following criteria: non-blastoid/pleomorphic variant, Ki-67 of 15-30%, white blood cell count of 15-30 x 10^9/L, lymph nodes ≤5 cm, TP53 mutated or wild type, del17p, MYC positive, complex karyotype, presence of KMT2D, BIRC3, or ≥1 other somatic mutations, and were asymptomatic without any clinical indication to start systemic therapy. Major exclusion criteria included significant disease-related symptoms, blastoid/pleomorphic variants, Ki-67 >30%, bulky tumors >5 cm. Patients received ibrutinib 560 mg P.O. daily in 28-day cycles and continued until progression, transformation, drug intolerance, or up to 5 years. The primary endpoint was progression-free survival (PFS). Secondary endpoints were safety, response rate, and duration of response (DOR). Response was measured using the Lugano criteria. It is expected that the current trial will achieve a median PFS time of about 18 months, which would be an improvement over PFS reported on high-risk patients under a watch and wait approach. The median follow-up time was 23.4 months.

Results: Twenty patients were enrolled (Table 1). The median age was 60.5 years (range 38-79). Most were male (n=15/20). At baseline, 13 patients (65%) had bone marrow involvement and 15 patients (75%) had gastrointestinal tract involvement. Seven patients (35%) had TP53 alterations. One patient was not evaluable for response due cessation of therapy after less than 1 cycle due to new onset atrial fibrillation. Among 19 evaluable patients, the best overall response rate was 94.7% (n=18/19). Of those who had a positive PET at baseline and were evaluable for PET response, 92.9% (n=13/14) achieved a PET complete response (CR). Of those with bone marrow involvement at baseline, 30.7% (n=4/13) achieved CR by flow cytometry. Of those with baseline gastrointestinal tract involvement, 33.3% (n=5/15) achieved histologically confirmed CR. The median number of cycles received was 16 (range 0-32). The median PFS and DOR were not reached. Seven patients discontinued therapy: atrial fibrillation (n=3), progressive disease (n=1), infection (n=1), lung cancer (n=1). The most frequent grade 3 toxicities were diarrhea (n=2, 10%), atrial fibrillation (n=1, 5%), infection (n=1, 5%), mucositis (n=1, 5%), and syncope (n=1, 5%). No grade 4 toxicities occurred. No deaths on study occurred.

Conclusions: Ibrutinib demonstrated significant efficacy with manageable toxicities in previously untreated patients with high-risk smoldering MCL.

Disclosures: Gaulin: ADC Therapeutics: Consultancy; DeciBio: Consultancy. Jain: AstraZeneca: Consultancy, Honoraria. Iyer: Yingli: Consultancy, Research Funding; Drenbio: Research Funding; Salarius: Consultancy; Pfizer: Research Funding; Ono: Research Funding; Astra Zeneca: Research Funding; Legend: Research Funding; Acrotech: Consultancy, Research Funding; Innate: Research Funding; CRISPR: Consultancy, Research Funding; Merck: Research Funding; Seagen: Consultancy, Research Funding; CuraBio: Speakers Bureau; American Society of Hematology: Speakers Bureau; American Society of Transplant and Cellular Therapy: Speakers Bureau. Lee: Takeda: Research Funding; Korean Society of Cardiology: Honoraria; Seagen Inc.: Research Funding; Olson Research: Honoraria; Oncternal Therapeutics: Research Funding; Pharmacyclics: Research Funding; Janssen: Honoraria; Guidepoint: Honoraria; Deloitte: Honoraria; Curio Sciences: Honoraria; Century Therapeutics: Consultancy; Celgene: Research Funding; Cancer Experts: Honoraria; Bristol-Myers Squibb: Research Funding; Aptitude Health: Honoraria. Vega: Geron: Research Funding; Allogene: Research Funding. Flowers: Allogene: Research Funding; Iovance: Research Funding; Denovo Biopharma: Consultancy; Takeda: Research Funding; Sanofi: Research Funding; Ziopharm: Research Funding; Cellectis: Research Funding; Karyopharm: Consultancy; Cancer Prevention and Research Institute of Texas: Research Funding; Bayer: Consultancy, Research Funding; Jannsen Pharmaceuticals: Research Funding; N-Power Medicine: Consultancy, Current holder of stock options in a privately-held company; Amgen: Research Funding; Guardant: Research Funding; Morphosys: Research Funding; Adaptimmune: Research Funding; Nektar: Research Funding; Kite: Research Funding; Beigene: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Burroghs Wellcome Fund: Research Funding; Abbvie: Consultancy, Research Funding; Foresight Diagnostics: Consultancy, Current holder of stock options in a privately-held company; Celgene: Consultancy, Research Funding; Genmab: Consultancy; Genentech Roche: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Pharmacyclics: Research Funding; Pharmacyclics Jansen: Consultancy; SeaGen: Consultancy; Spectrum: Consultancy; 4D: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; TG Therapeutics: Research Funding; Xencor: Research Funding; V Foundation: Research Funding; National Cancer Institute: Research Funding; Acerta: Research Funding; CPRIT Scholar in Cancer Research: Research Funding. Wang: Loxo Oncology: Research Funding; Juno Therapeutics: Research Funding; Genentech: Research Funding; Celgene: Other: Travel, Research Funding; WebMD: Honoraria; Oncology Specialty Group: Honoraria; Nurix: Honoraria; NIH: Honoraria; Moffit Cancer Center: Honoraria; MJH Life Sciences: Honoraria; MD Education: Honoraria; Meeting Minds Experts: Honoraria; Medscape: Honoraria; IDEOlogy Health: Honoraria; i3Health: Honoraria; Genmab: Honoraria, Research Funding; Eastern Virginia Medical School: Honoraria; Dava Oncology: Honoraria, Other: Travel; CAHON: Honoraria; Bantam Pharmaceutical: Honoraria; VelosBio: Consultancy, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Pepromene Bio: Consultancy; Parexel: Consultancy; Oncternal: Consultancy, Research Funding; Milken Institute: Consultancy; Miltenyi Biomedicine: Consultancy; Merck: Consultancy, Honoraria; Eli Lilly and Company: Consultancy, Research Funding; Leukemia & Lymphoma Society: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria, Other: Travel, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; InnoCare: Consultancy; Genentech: Consultancy; DTRM Biopharma (Cayman) Limited: Consultancy; Deciphera: Consultancy; Bristol Myers Squibb: Consultancy, Honoraria; BioInvent: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Be Biopharma: Consultancy; AstraZeneca: Consultancy, Honoraria, Other: Travel, Research Funding; Amphista Therapeutics Limited: Consultancy; ADC Therapeutics America: Consultancy; Acerta Pharma: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; OncLive: Honoraria; Studio ER Congressi: Honoraria; Physicians Education Resources (PER): Honoraria, Other: Travel; Scripps: Honoraria; Practice Point Communications (PPC): Honoraria; Molecular Templates: Research Funding; Vincerx: Research Funding.

OffLabel Disclosure: Ibrutinib in previously untreated smoldering mantle cell lymphoma

*signifies non-member of ASH