This ongoing trial comparing two regimens for auto transplant reveals that outcome is thus far nearly identical in the two groups of patients. The intermediate-dose patients (100 mg of melphalan for each of 3, out-patient transplants) suffered less toxicity. Dr. Ludwig suggests that this reduced dose of melphalan should be beneficial for patients who are more elderly and at higher risk for side effects.
Prospective, Randomized Comparison between Double Transplantation (T) with Melphalan (200 mg/m2) and Triple T with Intermediate Dose Melphalan (100 mg/m2) in Patients with Multiple Myeloma (An Interim Analysis). Session Type: Poster Session, Board #312-III
Heinz Ludwig, Werner Linkesch, Hedwig Kasparu, Otto Krieger, Ivan Spicka, Gunther Gastl, Richard Greil, Johannes Drach, Josef Thaler, Ingrid Kuhn, Niklas Zojer, Axel Hinke Department of Medicine I, Wilhelminen Hospital, Vienna, Austria; Department of Haematology, Medical University Graz, Graz, Austria; Department of Internal Medicine I, Elisabethinen Hospital, Linz, Austria; Department of Internal Medicine I, Charles University, Prague, Czech Republic; Department of Oncology and Hematology, University Innsbruck, Innsbruck, Austria; Department of Internal Medicine III, Hospital Salzburg, Salzburg, Austria; Department of Internal Medicine, Medical University Vienna, Vienna, Austria; Department of Internal Medicine III, Hospital of the Mercy Sisters, Wels, Austria; Schering-Plough Austria, Traiskirchen, Austria; WISP Research Institute, Langenfeld, Germany
In this study we compare the efficacy and toxicity of double T with M 200 with triple T using M 100 in newly diagnosed pts with MM. 175 pts have as yet been enrolled and 135 have been randomized after VAD induction treatment and stem cell collection to either tandem or triple transplantation. Reasons for non-randomization were too early for T (n=22), PD after induction (n=5), early death (n=3), toxicity (n=3), pt. refusal (n=3), and others (n=4). Median age of the 135 pts randomized was 59 years (range: 27-70 years). Stage I: 8%, stage II: 17%, stage III: 75%, Paraprotein Isotypes: IgG: 55%, IgA: 25%, IgD: 2%, IgM: 1%, Light chain: 17%. Induction treatment: 3 cycles of VAD; stem cell priming: IEV (ifosfamide (2g/m2)-etoposide (150mg/m2), d1-3; epirubicin (50mg/m2), d1) and G-CSF (5mg/kg) from d4. Conditioning regimen: M 200 mg/m2 or M 100 mg/m2 plus G-CSF; day 5 until WBC >2000/ml. Pts with SD after T were subsequently randomized to interferon 3MU, TIW (Schering Plough) plus prednisone (25mg, po., TIW), or interferon alone. QoL was assessed with the EORTC QLQ C30 instrument. Chi test for trend was used for comparison of response and survival endpoints were estimated by the Kaplan-Meier product limit method. Response rates after VAD were CR: 11%, PR: 65%, SD: 22% and PD: 2%. Median time from start of VAD to start of T was 137 in the double and 139 days in the triple T arm. Response rates did not differ between pts treated with double or triple T (CR: 47% vs. 43%, PR: 47% vs. 47%, SD 2% vs. 6%, PD: 4% vs. 4%, p=0.60, respectively). Median PFS for both groups combined was 36 mos, but showed a tendency for shorter PFS in pts on triple T (23 mos. vs. 37.5 mos; HR 1.26, 95% CI: 0.72-2.23, p=0.21). Median of OS has not been reached yet, but did not differ between both groups. Hematological toxicity was similar in both groups. There was a tendency for more grade 2-4 mucositis and for grade 3-4 vomiting, nausea, and fatigue in the double T group. Global QoL (questions 29 and 30) was comparable between both groups, before (5 (2.5-6.5) vs. 5 (4.5-6)) and after double (5.8 (3-8.5) or triple T (6 (2.5-7)). In conclusion, triple T with intermediate dose M resulted in similar response rates, slightly shorter PFS but similar OS and was associated with less mucositis and slightly less vomiting, nausea and fatigue.
Abstract #3083 appears in Blood, Volume 108, issue 11, November 16, 2006