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3778 Flat Dose Intravenous Immunoglobulin Primary Infection Prophylaxis in Multiple Myeloma Patients on Bispecific Antibody Therapy: Vanderbilt Experience

Program: Oral and Poster Abstracts
Session: 905. Outcomes Research—Lymphoid Malignancies: Poster II
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Adverse Events
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Naimisha Marneni, MBBS1*, Bhagirathbhai Dholaria, MBBS2, Salyka Sengsayadeth, MD3*, Eden Ayele Biltibo, MD, MS1, Vivek Patel, MD3, Shakthi Bhaskar, MD3, Reena Jayani, MD3, Jill Gilbert, MD1*, Jordan Berlin4*, Ashwin Kishtagari, MBBS5, Sanjay Mohan, MD, MSCI6, David Morgan, MD3*, Olalekan O. Oluwole, MBBS3, Bipin N. Savani, MD3, Adetola A. Kassim, MBBS, MS7 and Muhamed Baljevic, MD6*

1Vanderbilt University Medical Center, Nashville, TN
2Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN
3Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN
4Dept of Hematology/Oncology, Vanderbilt University Medical Center, Nashville
5Division of Hematology & Oncology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Franklin, TN
6Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
7Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN


Bispecific antibodies (BsAbs) are novel immunotherapeutic agents with prolific anti-multiple myeloma (MM) efficacy in highly relapsed/refractory disease (RRMM). They have been associated with profound and prolonged hypogammaglobinemia which represents a unique challenge regarding increased risk of serious (sometimes fatal) infections. Though IVIG has historically been dosed at 0.4g/kg for secondary prophylaxis, there is still uncertainty in optimal timing, schedule and frequency of supplementation in MM patients. At Vanderbilt University Medical Center, we have adopted a flat dose 10g IVIG prophylaxis schedule, which on average delivers ~36% of historical, weight-based dosing. At present, expert recommendations advise IVIG replacement every 4 weeks in recipients of BsAb starting the second month of therapy and continuing until the end of therapy or until serum IgG levels reach > 400 mg/dL, whichever is longer (Mohan M et al. Br J Haematol.2023;00:1–11). Considering that MM BsAbs are currently used with continued dosing schedule, adoption and anticipated new BsAb approvals are increasing, IVIG has previously been on national/global shortage (occasionally unavailable), IVIG replacement during hypogammaglobulinemia represents a crucial aspect of adequate infection prophylaxis in MM, we explored the impact of our institutional 10g IVIG prophylaxis on infection rates in RRMM patients receiving BsAbs. Prior studies with comparable BsAbs reported Grade (G) ≥3 infection rate of 32-45% and 18%, in anti-BCMA and anti-GPRC5D BsAbs, respectively. In these trials, overall, 14-53% of patients received IVIG prophylaxis.


We performed a retrospective review using electronic medical record of RRMM patients receiving anti-BCMA or anti-GPRC5D BsAbs from Jan 2019 to Dec 2022, either on clinical trials or as a standard of care at our institution. The inclusion criteria were minimum of two months of BsAb therapy, and the use of at least one month of monthly IVIG prophylaxis for serum IgG < 400 mg/dL. All patients were also on baseline valacyclovir, trimethoprim-sulfamethoxazole and levofloxacin prophylaxis. Routine disease and treatment specifics as well as infection rates and grades were collected. Infections were defined as mild (infections treated outpatient), moderate (required hospital admission) or severe (hospital admission with intensive care unit level of care), next to also being graded by CTCAE v5 with the rest of hematologic and non-hematologic adverse events (AEs).


A total of 30 patients with RRMM were identified. Table 1 illustrates the demographic and disease specifics: 79% received a median (range) of 4 (2-7) lines of prior therapy, over half were penta-class exposed, 27% were triple and quad refractory, 67% received a prior autologous stem cell transplant and 17% underwent prior treatment with BCMA targeting CAR-T therapy. All except 2 patients received BsAb therapy on clinical trials. Anti-GPRC5D BsAb was used to treat 60% of patients, while the rest (40%) received anti-BCMA BsAb, all of which were given for a median of 27 (12-45) months (Table 1). Overall, 30% of patients had one infectious episode, while 43% had ≥2. Viral infections (57%) were twice as common as bacterial (30%) (Table 2). Infections were mild in 60%, moderate in 23%, and severe in 6.6% of patients. We observed 27% rate of G ≥3 infectious complications. Patients had a median (range) IgG at diagnosis of 1284(196-5431), and 499(210-2246) at the time of onset of first infection (IgG values at the start of BsAb therapy, at first and at ≥2 infections are outlined in Table 2). The rate of G ≥3 neutropenia and lymphopenia was 6.6% and 30% respectively. There were 2 (6.6%) sepsis related deaths, one each with anti-BCMA and anti-GPRC5D BsAbs. Table 2 also describes severity and the rates of cytokine release syndrome and neurotoxicity.


We observed relatively lower rate of severe or ≥ G3 infectious events with 10g flat IVIG dosing schedule. While our results represent a small, single-institutional cohort of predominantly anti-GPRC5D treated RRMM patients and require prospective validation in a randomized (IVIG 10g vs 0.4g/kg body weight) fashion, they demonstrate feasibility of reduced level dosing of a critical resource such as IVIG, in the fast expanding, national/global BsAb-based MM armamentarium.

Disclosures: Dholaria: Poseida: Research Funding; gamida cel: Consultancy; Molecular Templates: Research Funding; AstraZeneca: Research Funding; Pluri Biotech: Consultancy; Boxer Capital: Consultancy; Ellipsis pharma: Consultancy; Adicet: Research Funding; Lumanity: Consultancy; Allovir: Research Funding; Takeda: Research Funding; BMS: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Poseida: Research Funding; Orca Bio: Research Funding; MEI: Research Funding; Atara: Research Funding; NCI: Research Funding; Angiocrine: Research Funding; BEAM therapeutics: Consultancy; Arivan: Consultancy; Pfizer: Research Funding; ADC therapeutics: Consultancy, Honoraria; Gilead: Research Funding; Wugen: Research Funding. Sengsayadeth: Amgen: Research Funding. Biltibo: BeiGene: Honoraria. Kishtagari: Geron Corporation: Membership on an entity's Board of Directors or advisory committees; Servier Pharmaceuticals: Consultancy; CTI BioPharma Corp., a Sobi company: Speakers Bureau. Mohan: Karyopharm, Astex, Incyte, Kartos, Ichnos, NCCN: Research Funding. Oluwole: Pfizer: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company/ Gilead: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; Caribou: Consultancy; Epizyme: Consultancy; Gilead: Consultancy, Honoraria; Cargo: Consultancy; AbbVie: Consultancy; ADC: Consultancy, Speakers Bureau; Nektar: Consultancy; Novartis: Consultancy; TGR: Consultancy; Allogene: Research Funding. Savani: Takeda Development Center Americas, Inc. (TDCA): Current Employment. Baljevic: Cardinal Health: Consultancy; AbbVie: Consultancy; Janssen Biotech: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Parexel: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH