A Phase II Study of the Efficacy and Safety of Lenalidomide, Subcutaneous Bortezomib and Dexamethasone (RVD) Combination Therapy for Patients with Newly Diagnosed Multiple Myeloma: Promising Activity and Manageable Toxicity, Including in High Risk Disease

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.1981-1981
• Main Authors: Laubach, Jacob, Yee, Andrew J, Rosenblatt, Jacalyn, Matous, Jeffrey V, Farber, Charles M., Openshaw, Thomas H., Maegawa, Rodrigo O., Tsai, Michaela L., Ghobrial, Irene M., Bianchi, Giada, Rawal, Bhupendra, Dipietro, Heidi, Cummings, Kristen, Harran, John, O'Gorman, Peter, Scott, Kathleen, Fitzpatrick, Kathleen, Abovich, Jennifer, Baker, Hannah, Savell, Alexandra, Hansen, Joshua, Richardson, Paul
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-116280

Introduction: Patients (pts) with newly diagnosed multiple myeloma (MM) are commonly treated with the standard of care combination of lenalidomide (Len), bortezomib (Bz), and dexamethasone (Dex), also known as RVD. A recent randomized phase 3 study found that the addition of Bz to Len and Dex significantly increased median overall and progression free survival as well as response rate (Durie et al. Lancet 2017). Mild to moderate peripheral neuropathy (PN) is commonly reported with Bz use, although lower rates of PN have been reported with subcutaneous (SC) administration of single agent Bz compared with IV Bz (Moreau et al. Lancet Oncol 2011). Here we present preliminary results of a multi-center, open-label, single arm phase II trial of Len, SC Bz, and Dex in pts with newly diagnosed MM. Maintenance was risk-stratified, with high risk patients (defined as those with high risk cytogenetics (del17p, t(4:14), t(14;16)) or ISS stage II or III) receiving Bz in addition to Len. Primary endpoints included 1) overall response rate (ORR) after 4 induction cycles, 2) best response to induction therapy, and 3) rate and severity of PN during induction therapy. Methods: Patients enrolled in this study were newly diagnosed with active MM as defined by the revised IMWG criteria (Rajkumar et al. Lancet Oncol 2014). Protocol specified induction treatment consisted of 21-day cycles with Len 25 mg on days 1-14, SQ Bz 1.3 mg/m2 days 1, 4, 8, and 11, and Dex 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12. Stem cell mobilization followed induction cycle 4 and patients subsequently proceeded to either high dose melphalan and autologous stem cell transplant (ASCT) or 4 additional cycles of induction therapy based on patient preference with provider input. Following ASCT or completion of the 8th induction cycle pts proceeded to risk-stratified maintenance therapy. Maintenance consisted of 28-day cycles of therapy with Len on days 1-21 for all patients, while those pts defined as high-risk also received SC bortezomib Bz on days 1 and 15. Patients remained on maintenance therapy until progression, unacceptable toxicity, or withdrawal from protocol-directed treatment. Response was based on the IMWG uniform criteria (Rajkumar et al. Lancet Oncol 2011) and toxicities were graded based on the NCI-CTCAE V4. Correlative samples of blood and bone marrow for genomics and proteomics were collected from baseline and then throughout the study, and are currently being analyzed. Results: Forty-five