VDTPACE As Salvage Therapy For Heavily Pretreated MM Patients

DTPACE is a combination chemotherapy regimen using dexamethasone, thalidomide and a 4-day (d) continuous infusion of cisplatin, doxorubicin, cyclophosphamide, and etoposide. It integrates components of CAD (cyclophosphamide, doxorubicin, dexamethasone) and DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin), both of which were components of the Arkansas Total Therapy 2 (TT2) approach to multiple myeloma (MM) treatment. Most recently, DTPACE has been combined with bortezomib (VDTPACE) as induction and consolidation after tandem transplantation as part of Total Therapy 3 (TT3). Limited experience suggests that DTPACE,  reduces disease burden as a salvage regimen for aggressive MM or plasma cell leukaemia (PCL) resistant to conventional therapies. In heavily pretreated myeloma, DTPACE has advantages as it uses a number of agents to which the typical MM patient has not previously been exposed, some of which penetrate the blood brain barrier and thus may be effective for leptomeningeal myeloma. On the contrary not enough data are available about the role of VDTPACE as salvage therapy in MM patients. To this scope, we identifed a total of 16 patients who received VDTPACE for relapsed/refractory MM. All patients were heavily pretreated (median three prior regimens, range 1-6; prior autologous stem cell transplant [ASCT] 38%). Five of these patients (31%) had developed very aggressive MM complications, such as extramedullary disease. The VDTPACE regimen consisted of high-dose dexamethasone (40 mg orally daily for 4 d) and a 4-d continuous infusion of cisplatin (10 mg/sqm/d), doxorubicin (10 mg/sqm/d), cyclophosphamide (400 mg/sqm/d) and etoposide (40 mg/sqm/d). Bortezomib was administered intravenously at 1.0 mg/sqm (d 1,4,8,11) and thalidomide was given orally at 100 mg daily. A total of 4 cycles of VDTPACE were administered every 4-6 weeks. Response was graded using the International Myeloma Working Group uniform response criteria. Overall response rate was 63% (very-good partial response 7%, partial response 56%) with stable disease in an additional 12% of patients. Median progression-free survival (PFS) was 7 months (95% confdence interval [CI]:4.0 - 9.9). VDTPACE is an intensive regimen which was given in our cohort on an inpatient basis because myelotoxicity is common. The  rates of grade 3-4 neutropenia (56%) and febrile neutropenia (56%) were high although GCSF support was used routinely as prophylaxis. The most common non-haematological toxicities were grade 1-2 metabolic abnormalities that were easily corrected. VDTPACE is an effective salvage therapy for heavily pretreated MM patients. In the era of new targeted, biologically active agents against MM, there are now many more options for refractory and relapsed disease. Unfortunately, many of these newer agents are costly and awaiting approval in a number of countries. Consequently, alternative therapies are needed. Although the overall response rate of 63% in this poor prognosis cohort is more than promising, the PFS is short, suggesting the best role for VDTPACE is in bridging to defnitive therapy, such as allo-transplantation.

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