Multiple Myeloma

Abstract

1995 Subcutaneous Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma: Part 2 Safety and E cacy Update of the Open-Label, Multicenter, Phase 1b Study (PAVO) Ajai Chari, MD, Maria-Victoria Mateos, MD, PhD, Niels W. C. J. van de Donk, Jonathan L. Kaufman, MD, Philippe Moreau, Albert Oriol, MD, Torben Plesner, MD, DSc, Lotfi Benboubker, MD, Hareth Nahi, MD, PhD, Jie Tang, Peter Hellemans, Brenda Tromp, MSc, Pamela L. Clemens, PhD, Andrew Farnsworth, Visit http://www.bloodjournal.org/content/132/ Suppl_1/1995 for a complete list of contributor affiliations and full graphics. Introduction: man IgGκ anti-CD38 monoclonal antibody with a direct on-tumor and immunomodulatory mechanism of action. DARA (16 mg/kg administered intravenously [IV]) is approved in many countries as monotherapy and in combination with standard of care (SOC) treatment regimens for patients with relapsed/refractory (RR) multiple myeloma (MM) and newly diagnosed MM. Three phase 3 studies have now demonstrated that DARA in combination with SOC treatment doubles complete response (CR) rates, triples minimal residual disease-negative rates, and reduces the risk of progression or death by at least 50% vs SOC alone. The median durations of the first, second, and subsequent DARA IV infusions are 7.0, 4.3, and 3.4 hours, respectively. To determine whether the duration of infusion can be shortened without coman open-label, multicenter, phase 1b clinical trial (PAVO; NCT02519452) was conducted to evaluate a subcutaneous (SC) formulation of DARA with recombinant human hyaluronidase enzyme PH20 ogy, Halozyme, Inc.) in patients with RRMM. Part 1 of the study revealed that a mix-and-deliver SC administration was well tolerated, with low rates of infusion-related reactions (IRRs) and similar stract 1149). Here, we present updated safety and where a concentrated, pre-mixed SC co-formulation of DARA and rHuPH20 (DARA SC) was evaluated in patients with RRMM. Methods: ceived ≥2 prior lines of therapy, including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD). In Part 2 of the study, a concentrated co-formulation of DARA (1,800 mg) and rHuPH20 (30,000 U; in 15 mL) in a single, premixed vial was administered over 3 to 5 minutes by manual SC injection into the abdomen. DARA SC was given QW during Cycles 1-2, Q2W during Cycles 3-6, and Q4W thereafter in 28-day cycles. Preand/or post infusion medications included acetaminophen, diphenhydramine, montelukast, and methylprednisolone. Co-primary endpoints were safety and Ctrough QW dosing. Secondary endpoints included the overall response rate (ORR) and CR rate according to the International Myeloma Working Group response criteria. Results: ber 13, 2017, 25 patients were enrolled in Part 2 of the study. Patients received a median of 3 (range: 2-9) prior lines of therapy, with 56% double refractory to both PI and IMiD. No treatment discontinuations occurred due to treatment-emergent adverse events (TEAEs). The most common (≥20%) TEAEs included lymphopenia (32%), thrombocytopenia (24%), fatigue, asthenia, back pain, diarrhea, nausea, headache, and viral upper respiratory tract infection (20% each). The incidence (16%) and severity of IRRs (mostly grade 1-2) with DARA SC was low, the majority of which occurred on Cycle 1 Day 1, and no discontinuations due to IRRs were observed. Transient grade 3 hypertension was reportMultiple Myeloma J Adv Pract Oncol 2019;10(suppl 2):4-9 https://doi.org/10.6004/jadpro.2019.10.2.16 Th is ar tic le is dis tri bu te d u nd er th e t er m s o f t he Cr ea tiv e C om m on s A ttr ibu tio n N on -C om m er cia l N on -D er iva tiv e L ice ns e, wh ich pe rm its un re str ict ed no nco m m er cia l a nd no nde riv at ive us e, dis tri bu tio n, an d r ep ro du cti on in an y m ed ium , p rov ide d t he or igi na l w or k i s p ro pe rly ci te d.