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2416 Preliminary Results of Daratumumab, Cyclophosphamide, Thalidomide and Dexamethasone: A Quadruplet Intensified Treatment for Newly Diagnosed Multiple Myeloma (NDMM) Transplant Eligible (TE) Patients

Program: Oral and Poster Abstracts
Session: 731. Clinical Autologous Transplantation: Results: Poster II
Hematology Disease Topics & Pathways:
therapy sequence, multiple myeloma, Diseases, Combinations, Therapies, Plasma Cell Disorders, Lymphoid Malignancies, Clinically relevant
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Edvan De Queiroz Crusoe, MD, PhD1,2, Marco Aurelio Salvino, MD, PhD3,4, Sarah Queiroz Silva, MD5*, Herbert Henrique de Melo Santos, MD6*, Allan de souza Santos, BS7*, Alessandro de M. Almeida, MD8,9, Lucas de Oliveira Vieira, MD10*, Cleverson Alves Fonseca, Pham11*, Larissa Ferreira Lucas, MD12*, Joanna Leal, MD13*, Mariane Melo Santos, BS, MsC14*, Juliana Andrade Santos, MD15*, Elisangela Adorno, Pham, PhD16*, Vania T. M. Hungria, MD, PhD17 and Maria da Gloria B. Arruda, MD, PhD4,18*

1Rua Dra Doutro Vianna S/n, Universidade Federal da Bahia- Hospital Universitario, Salvador, Brazil
2Hematology department- D'or Oncologia, Clinica CEHON Rede D'or Oncologia, Salvador, Brazil
3Hematology and Bone Marrow Transplantation UNIT, Rede D'or Oncologia, Salvador, Brazil
4Federal University of Bahia, Salvador, Brazil
5Hematology, Rede D'or Oncologia- Salvador, Salvador, Brazil
6Immunology, molecullar and Cytometry Laboratory- ICS, Federal University of Bahia, Salvador, Brazil
7Immunology, mollecular and cytometry Laboratory- ICS, Federal University of Bahia, Salvador, Brazil
8Stem Cell Transplant Unit, Federal University of Bahia, Salvador, Brazil
9Hematology and Bone Marrow Unit, Rede D´or Oncologia, salvador, Brazil
10Nuclear Medicin, Rede D'or Oncologia, Salvador, Brazil
11Faculty of Pharmacy, Federal University of Bahia, Salvador, Brazil
12Hematology, CLinica CEHON Rede D'or Oncologia, salvador, Brazil
13Hematology, Hematology Rede D'or oncologia, salvador, Brazil
14Immunology, mollecullar and cytometry Laboratory- ICS, Federal University of Bahia, salvador, Brazil
15Hematology, Clinica CEHON Rede D'or oncologia, Salvador, Brazil
16Faculty of Phamacy, Federal University of Bahia, salvador, Brazil
17Department of Hematology, Clinica São Germano and Santa Casa Medical School, São Paulo, Brazil
18Hematology, Clinica CEHON Rede D'or Oncologia, salvador, Brazil

Background: The inclusion of the CD38-targeting antibody daratumumab (Dara) increases the depth and duration of the response, as demonstrated by Dara-VTd and Dara-VRd protocols to treat NDMM - TE patients (pts). However, the access to new drugs is a challenge for some countries in Latin America. There are many induction protocols and one of the most used inductions worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)- (CTd). We hypothesized that the combination of daratumumab and CTd (Dara-CTd) could be safe and allow deeper activity in NDMM TE pts. Objective: The primary endpoint was the attainment of VGPR after two consolidation cycles post-autologous stem cell transplantation (ASCT). Secondary endpoints were the overall response rate during all treatment phases and minimal residual disease (MRD), based on the International Myeloma Working Group (IMWG) criteria that includes the next-generation flow by the EuroFlow® and PET-CT and the safety profile. An exploratory endpoint was the analysis of the immunologic change in the lymphocyte profile during the treatment. Methods: This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: NDMM TE, creatinine clearance > 30 ml/min, normal cardiac, renal and liver function and the Easter Cooperative Oncology Group (ECOG) performance status = 0 - 2. The protocol scheme was Dara-CTd for up to four 28-day induction cycles: C-500mg oral (PO) on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, Dex at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 – 4, followed by ASCT. Consolidation was started at D+30 after transplant and all patients received up to four 28-day consolidation cycles: Dara at 16mg/Kg and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara at 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. All patients received antiviral, anti-pneumocystis and anti-thrombotic prophylaxis. Results: The first patient was enrolled in November 2018. A total of 21 pts were included, the median age being 56 (range 38 - 67 years), 18 (85%) were non-white, 3 (14%) had an R-ISS = 1, 12 (57%) had an R-ISS = 2 and 3 (14%), an R-ISS = 3. Five (24%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, 18 pts have completed induction, 12 have received transplants and 10 have completed D+90 post-transplant assessment. In an intention to treatment analysis, after the end of induction (cycle 4), 17 (95%) of the pts obtained > PR and 7 (33%) obtained VGPR or better. Ten patients have completed two consolidation cycles after transplant and 100% obtained > VGPR as best response, 8 (80%) obtained MRD = -10-5 negative remission by flow cytometry and 6 (60%) had negative PET-CTs. Five (50%) patients had both flow and PET-CT negativity. Two patients died from infection, one post-transplant, considered not related to the investigational agent, and another after consolidation, related to the investigational agent. The most common non-hematological adverse events (AEs) grades 3 and 4 before ASCT were neuropathy (n = 6), infusion reaction (n = 6), infection (n = 2), hypertension (n = 1) and rash (n = 1). Conclusion: This is the first study that combined daratumumab with CTd as induction for NDMM TE patients. This preliminary data has shown that the association of Dara-CTd achieved a deep response with a safety profile. Clinical trial information: NCT03792620.

Disclosures: De Queiroz Crusoe: Janssen: Research Funding.

*signifies non-member of ASH