Treatment outcome and prognostic factor analysis in transplant-eligible Chinese myeloma patients receiving bortezomib-based induction regimens including the staged approach, PAD or VTD

BACKGROUND: We have reported promising outcomes using a staged approach, in which bortezomib/thalidomide/dexamethasone was used only in 14 patients with suboptimal response to VAD (vincristine/adriamycin/dexamethasone) before autologous stem cell transplantation (ASCT). Here we compared the outcomes of the staged approach with frontline PAD (bortezomib/doxorubicin/dexamethasone) or VTD (bortezomib/thalidomide/dexamethasone) induction, and analysed prognostic factors for outcome. PATIENTS AND METHODS: Ninety-one transplant-eligible Chinese patients received three induction regimens prior to ASCT [staged approach (N = 25), PAD (N = 31), VTD (N = 35)]. and received thalidomide maintenance for 2 years post-ASCT. RESULTS: 43 (47.3%) patients had International Staging System (ISS) III disease. By an intention-to-treat analysis, the overall CR/nCR rate were 37.4% post-induction, and 62.6% post-ASCT. Five-year overall (OS) and event-free (EFS) survivals were 66% and 45.1%. There was no difference of the post-induction CR/nCR rate, EFS or OS between patients induced by these three regimens. Moreover, ISS III disease did not affect CR/nCR rates. Multivariate analysis showed that ISS and post-ASCT CR/nCR impacted OS while ISS and post-induction CR/nCR impacted EFS. CONCLUSIONS: These three induction regimens produced comparable and favorable outcomes in myeloma. The unfavorable outcome of ISS stage III persisted despite upfront/early use of bortezomib. CR/nCR predicted favorable survivals

Clofarabine and high-dose cytosine arabinoside in the treatment of refractory or relapsed acute myeloid leukaemia

Clofarabine (40 mg/m2/day × 5) and high-dose cytosine arabinoside (Ara-C, 1–2 g/m2/day × 5) were used in 10 men and 11 women, at a median age of 45 (22–62) years, with refractory (N = 4) and relapsed (N = 17) acute myeloid leukaemia, after a median of 3 (2–5) prior regimens. Grade 4 myelosuppression was observed in all cases, with two patients dying of bacterial sepsis. Nine patients achieved a complete remission. Disease status, number of prior therapies, and cytogenetic aberrations were not associated with the outcome. However, remission was only achieved with Ara-C at 2 g/m2/day and not 1 g/m2/day (9/15 versus 0/4, P = 0.03)

The Use of Clofarabine and Cytarabine Combination (CLARA) As Salvage Therapy for Relapsed and/or Refractory Acute Myeloid Leukemia (AML)

Abstract Abstract 1518 Patients with relapsed and/or refractory acute myeloid leukemia (AML) have a very dismal outcome and treatments are largely unsatisfactory. Salvage therapy is often limited by drug resistance and organ toxicities in patients who have already been exposed to multiple lines of chemotherapy. Clofarabine is a second generation nucleoside analogue with multiple mechanisms of action including inhibition of ribonucleotide reductase, suppression of DNA polymerase, direct DNA incorporation and induction of apoptosis. In this study, we evaluated the clinical outcome of patients with relapsed and/or refractory AML who received combination treatment of clofarabine and cytarbine (acronym CLARA) at Queen Mary Hospital in Hong Kong. The treatment with CLARA comprised clofarabine 40 mg/m2 and cytarabine 2 gm/m2 given intravenously for five days. For patients who relapsed after allogeneic hematopoietic stem cell transplantation (HSCT), CLARA was followed by the infusion of either BM or mobilized peripheral blood stem cells (PBSC) from the original donor and immunosuppression (cyclosporine A at 1.5 mg/kg twice daily) was given from day 8 after HSC infusion. All patients received standard anti-microbial prophylaxes and G-CSF support during neutropenia. Remission status was confirmed by bone marrow examination. Since 2009, a total of 55 patients have been recruited of whom 19 received CLARA at relapse after allogeneic HSCT. The median age of the patients was 45 years (range 20–64) and cytogenetic categorizations were favorable (N=7); intermediate (N=29) and unfavorable (N=14) in 50 evaluable patients. There were a median of two regimens (range 1–4) and five courses (range 1–12) of chemotherapy before CLARA. All patients developed grade 4 hematologic toxicity and 20% (no. of patients: grade 1–2=8; grade 3= 3) and 60% (grade 1–2=23; grade 3–4=10) developed dermatologic and liver toxicities. Six patients including three who relapsed after HSCT (out of 19 patients=16%) and three non-transplant patients (out of 36 patients=8%) died of treatment related mortality after CLARA (overall 11%). Twenty-seven patients (49%) achieved complete remission (CR) or CR with insufficient hematologic recovery (CRi). Patients who received CLARA for relapse post-HSCT had a higher CR/CRi (12 out 19 patients=63%) than the non-transplant patients (15 out of 36 patients=42%). The respective median disease-free (DFS) and overall-survivals (OS) of the post-HSCT relapse and non-transplant patients were 9.6 and 5.0 months (DFS) and 11.5 and 8.0 months (OS). CLARA is an effective salvage regimen for both post-HSCT relapse and non-transplant patients with tolerable side-effects. The optimal consolidation and maintenance strategies after CLARA would have to be further defined. Acknowledgments: Clofarabine was provided by a compassionate program from Sanofi-aventis Hong Kong Ltd. Disclosures: Off Label Use: Clofarabine. </jats:sec