Mitoxantrone and Melphalan as Conditioning Regimen for Autologous Stem Cell Transplant for Multiple Myeloma.

Beaven, Anne W.; Comeau, Terrance; Sharf, Andrew; Moore, Dominic T.; Serody, Jonathan; Shea, Thomas C.; Gabriel, Don A.

doi:10.1182/blood.V108.11.2945.2945

Abstract

High dose Melphalan (Mel) has demonstrated efficacy in the treatment of multiple myeloma (MM). Mitoxantrone (Mit), in combination with vincristine and prednisone, also has demonstrated activity in MM with the benefit of less cardiac toxicity than other standard regimens. In this trial Mel and Mit were combined as a transplant preparative regimen. Mit was given as a prolonged 6 hour infusion on 2 separate days to increase intracellular drug levels and decrease cardiac toxicity (

Kaminer et al. Cancer1990; 65, 2619–2623

;

Koc et al. Hematol Oncol2004;22:43–53

).

PATIENTS: 35 patients with a diagnosis of MM were enrolled between 9/98–6/02. Median age was 59 (range, 38–69); 60% had received ≥ 2 previous regimens (range, 1–6). The median time from diagnosis to transplant was 9 months (95% CI, 8–12 months). 57% had stage III disease and 26% stage II at diagnosis; median Beta-2 microglobulin was 3.6 mg/L (available in only 13 patients). All patients completed therapy with Mit 30mg/m²/day infused over 6 hours on days -6 and -5 and Mel 180mg/m² on day -1.

RESULTS: The median follow-up for survivors was approximately 45 months (range, 3–84 months). The median times to granulocyte and platelet engraftment were 11 days and 14 days respectively. 2 patients failed to engraft; 1 proceeded to allogeneic transplant, the other died on day 28 secondary to sepsis. The 100-day TRM was 2.9%. The median progression free survival (PFS) was 20 months (95% CI, 13–31) (Figure 1) with a median overall survival (OS) of 57 months (Figure 2). 4 patients are alive and progression free more than 48 months out from transplant. 8/35 (23%) of patients achieved a complete response (CR). Of the 8 patients who had a CR, 7 (20% of total patients) are still alive and progression free with a median follow-up of 39 months after transplant (range, 12 to 80 months). The achievement of a CR was significantly associated with longer PFS but not with OS. The mean CD34 count of infused cells was 4.92 ×10⁶/kg and did not appear to be significantly associated with CR rate, OS, or time to engraftment of platelets or granulocytes. Overall, therapy was well tolerated with a median of 8 days (range, 0–15) of any grade of mucositis and a median of 3 days of fever. The mean LVEF on MUGA was 64% pre-transplant and decreased to 58% post-transplant. 1 patient with diabetes and hypertension developed congestive heart failure after discharge from the hospital but with therapy the LVEF returned to normal.

CONCLUSION: The combination of Mel and infusional Mit is an effective regimen with 23% CR rate despite multiple previous therapies. The median OS of 57 months compares well to other transplant trials and patients who achieved a CR demonstrated better long-term PFS.