Prospective Randomized Trial of Len/Dex Induction Followed by Tandem MEL140 with Autologous Blood Stem Cell Transplantation and Len Maintenance Versus Continued Therapy with Len/Dex in Myeloma Patients Age 60–75 Years: Protocol-Defined Safety Analysis After 100 Patients
Authors: Straka Christian , Schäfer-Eckart Kerstin , Bassermann Florian , Hertenstein Bernd , Engelhardt Monika , Salwender Hans , Rösler Wolf , Langer Christian , Schilling Georgia , Knop Stefan , Brümmendorf Tim H , Metzner Bernd , Hebart Holger , Reichle Albrecht , Frickhofen Norbert , Heidemann Else , Ababei Juliana , Gerecke Christian , Jung Wolfram , Gramatzki Martin , Decker Thomas , Kropff Martin , Naumann Ralph , Hentrich Marcus , Walther Jochem , Bojko Peter , Dechow Tobias , Wandt Hannes , Hinke Axel , Einsele Hermann 
Published: October 2019

Abstract
Abstract 2012
In this trial (DSMM XIII) patients of age 60–75 years with newly diagnosed multiple myeloma having symptomatic and measurable disease were randomly assigned to either (A1) 3 cycles of Lenalidomide (25 mg po d1-21/28d) with low-dose Dexamethason (40 mg po d1, d8, d15, d22/28d), followed by stem cell mobilization and then further Len/Dex cycles until progression or (A2) 3 cycles of Len/Dex, followed by stem cell mobilization, tandem high-dose melphalan 140 mg/m2 with autologous blood stem cell transplantation and Len maintenance with 10 mg daily until progression. The maximum time of treatment was defined as 5 years. Antithrombotic prophylaxis consists of LMW heparin for 3 months in both arms. With continued Len/Dex (A1) antithrombotic prophylaxis is also continued after stem cell mobilization with either LMW herparin or aspirin, depending on risk factors. Here we report the severe adverse events (SAEs) after 100 patients who have completed at least 3 cycles induction therapy and the efficacy of stem cell mobilization.
149 patients with a median age of 68 years and a proportion of patients with age ≥70 years of 40%, have been randomized since March 2010. With the first 100 patients having completed 3 cycles of induction Len/Dex, 105 SAEs have been reported in 67 patients. SAEs consisted of infections (36), thromboembolic events (7), fever (6), syncope (5), renal failure (4), fractures (4), dyspnoe (4), heart failure (3), pain (3), hyperglycemia (3), rash (1), plasma cell leukemia (1), second malignancy (1) and others. The second malignancy was a melanoma in situ which was completely surgically removed and reported as a SUSAR. Nine patients have died, 2 during study treatment (progression 1, sepsis 1) and 7 off study (progression 4, heart failure 1, sepsis 1, unknown 1).
For stem cell mobilization, two alternative protocols were allowed. The decision was left open to the investigator. Either G-CSF only (lenograstim 10 μg/kg for 4 days or end of apheresis) or CE chemotherapy with G-CSF (cyclophosphamide 2500 mg/m2, etoposide 300 mg/m2 plus lenograstim 263 μg from day 5 until end of apheresis) were applied. Mobilization data from 75 patients are available. G-CSF only was used in 10 patients (13%) and resulted in a median of 5.3 × 106 CD34 positive cells/kg (range 1.5 – 8.9) collected with a median of 2 leukaphereses (range 1 – 4). CE plus G-CSF was used in 64 patients (85%) and resulted in a median of 7.5 × 106 CD34 positive cells/kg (range 2.0–38.0) collected with a median of 1 leukapheresis (range 1 – 4). In 2 patients (3%) stem cell mobilization failed after CE plus G-CSF.
Len/Dex induction therapy was associated with an acceptable tolerability and feasibility in elderly myeloma patients. Stem cell mobilization was successful in 97% of patients.

Disclosures:
Straka: Celgene: Consultancy, Honoraria, Research Funding. Off Label Use: Lenalidomide used for initial therapy in multiple myeloma.