DT-PACE

Abstract: Incorporation of novel biological agents has become the cornerstone of treatment in multiple myeloma. For the last 4 years we have adopted the more intensified approach, previously published as total therapy 3 by the Arkansas group and used it with local modifications. This study aims to evaluate the efficacy and safety of the Arkansas protocol-based treatment outside clinical trial in a tertiary medical center in Israel. We retrospectively analyzed 23 patients. Seventy-three percent of the patients achieved very good partial remission (VGPR) before autologous stem cell transplantation (ASCT). Eighty-six percent of the patients achieved at least VGPR after tandem ASCT. Two-year overall survival was estimated as 70%. Four patients died during treatment, one as a result of disease progression. We conclude that this protocol is effective and rather safe. Further clinical trials should assess which subgroups of patients would benefit most from this approach.

Abstract: Routine use of novel agents to treat newly diagnosed and relapsed multiple myeloma (MM) produces high response rates and improved survival. However, 15–20% of patients have suboptimal responses and their management remains challenging.1 Traditional regimens, such as DT‐PACE (dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, etoposide) and ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) are employed in patients with relapsed/refractory (RR) disease, and may bridge patients to autologous stem cell transplantation (ASCT).2-4 Originally developed to improve responses to traditional chemotherapy regimens, and enable stem cell mobilization,5-7 the role of infusional regimens in the context of novel agents is unclear, especially as recently reported series indicate relatively poor outcomes.8, 9 These regimens can be associated with significant toxicity,2 placing a burden on healthcare resources.10 We undertook a single‐centre retrospective analysis to assess the role of infusional regimens in RR MM patients to explore and identify features associated with clinical benefit. Relevant clinical information was obtained from electronic records. Overall response rate (ORR) and cytogenetic risk were assessed as per International Myeloma Working Group (IMWG) criteria (Table I).11 [Progression‐free (PFS) and overall survival (OS) were estimated using Kaplan–Meier and Cox regression methods (time‐dependent where appropriate)].

Abstract: Objective In this retrospective single center study we have looked into the transplant outcomes(overall survival OS, progression free survival PFS,GvHD) and the role of chimerism, DLI and pre-transplant characteristics in patients who had a suboptimal response (<12 months)to an autologous stem cell transplant for myeloma and underwent an Alemtuzumab T-cell depleted reduced intensity allograft(RIC). Methods 24 patients were salvaged with 2 cycles of DT-PACE and received a RIC transplant with Fludarabine, Melphalan and Alemtuzumab. All the patients received PBSC grafts, 8 patients had a sibling donor and 16 had a graft from a fully matched unrelated donor. The median follow up was 65.3 months (6-132 months). Results The median overall survival 55.4 months. DLI administration was associated with a trend towards better overall survival (p:0.05).Disease status at allo-HCT, PR or VGPR,ISS score and CMV serostatus were not significant predictors of OS and PFS. Full donor whole blood chimerism (>= 98%) at 3 months post-transplant was associated with PFS (p:0.04) but did not have a significant impact on OS(p:0.45). Conclusion Reduced intensity alemtuzumab conditioned allografts for myeloma after DT-PACE salvage chemotherapy is an efficient and low toxicity treatment for those who had a suboptimal response post autologous stem cell transplant for myeloma. This article is protected by copyright. All rights reserved.

Abstract: Blastoid morphology is a rare presenting feature of myeloma which is frequently seen in patients with extramedullary myeloma and is associated with poor clinical outcome. Cell cycle active agents can be effective as treatment for aggressive myeloma and their activity enhanced by using them in combination with the anti-angiogenic agent thalidomide. DT-PACE is an example of such a regimen which we have used to treat 26 relapsed and or refractory patients with extramedullary/blastoid myeloma. The overall response rate (complete response/PR) was 59%, but despite these initial good responses, patients had a short progression free survival (PFS) and overall survival (OS). A subgroup of patients who proceeded to autologous stem cell transplant (ASCT) have a trend towards a better PFS and OS when compared with the group receiving chemotherapy alone (PFS = 10 vs. 3 months P = 0.273 and OS 10 vs. 7 months P = 0.235). Interestingly of the group who received ASCT consolidation three patients remain alive beyond 18 months. In conclusion, the clinical outcome of this group of cases is poor even when treated with the intensive regimen DT-PACE; however, a subgroup can do well if DT-PACE is consolidated by ASCT.