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54th ASH Annual Meeting
News
54th ASH Annual Meeting
Steve Gschmeissner/Science Photo Library
New IMiD for multiple myeloma
Published Online December 21, 2012 http://dx.doi.org/10.1016/ S1470-2045(12)70578-8 The annual meeting of the American Society of Hematology was held in Atlanta, GA, USA, on Dec 8–11, 2012
Pomalidomide plus low-dose dexamethasone is an effective treatment for refractory multiple myeloma according to results of a phase 3 open-label randomised trial. Meletios Dimopoulos (Athens, Greece) and colleagues found patients refractory to bortezomib, thalidomide, or lenalidomide treated with pomalidomide plus dexamethasone had a significant improvement in progression-free survival (HR 0·45, p<0·001) and overall survival (HR 0·53, p<0·001) compared with patients treated with high-dose dexamethasone alone. Further support for pomalidomide was also shown by Tomer Mark (New York, NY, USA) and colleagues, who reported good efficacy in a phase 2 trial of patients with heavily pretreated multiple myeloma using a combination of pomalidomide, dexamethasone, and clarithromycin, and by Jatin Shah (Houston, TX, USA) and colleagues who showed good responses in a phase 1/2 trial combining this particular IMiD with carfilzomib in relapsed/refractory with multiple myeloma.
Arsenic for APL The first head-to-head phase 3 trial of ATRA plus arsenic trioxide versus ATRA plus idarubicin has been done in patients with newly diagnosed acute promyelocytic leukaemia in hospitals in Italy and Germany. Francesco Lo-Coco (Rome, Italy) and colleagues found arsenic trioxide was non-inferior to chemotherapy in this setting and had a more tolerable toxicity profile. 2-year event-free survival was 97% vs 86·7% (p=0·03) for the arsenic trioxide regimen versus standard chemotherapy, respectively.
FLT3-directed therapy A multinational group lead by Jorge Cortes (Houston, TX, USA) have found the FLT3 tyrosine kinase inhibitor, quizartinib causes the highest singleagent responses seen to date in 112
relapsed or refractory patients with acute myeloid leukaemia. Responses were seen in both patients older than 60 years (N=134; composite complete remission of 54% for FLT3-IAD+ patients, 32% for FLT3-IAD– patients) and in patients who had failed secondline salvage chemotherapy or stem-cell transplantation (N=137; composite complete remission of 44% for FLT3-AD+ patients, 34% for FLT3-IAD– patients). Although drug doses were different for male and female patients, adverse events were manageable and could be mitigated with dose modifications.
No role for radiotherapy Results of a phase 3 non-inferiority trial (John Radford, Manchester, UK, and collegaues) have shown patients with early stage Hodgkin’s lymphoma with a negative PET scan after three cycles of ABVD have a good prognosis and do not require further treatment with involved field radiotherapy (IFRT). After ABVD therapy, researchers randomised PET-negative patients to either IFRT or no further treatment, and PET-positive patients to an additional cycle of ABVD and IFRT. All PET scans were reviewed centrally. 3-year overall survival was 97·0%, 99·5%, and 93·9%, respectively, for the three groups.
New options for DLBCL Up to 40% of elderly patients with diffuse B-cell lymphoma relapse after treatment with R-CHOP. Two phase 2 trials done in Europe have shown the efficacy of induction R-CHOP can be improved by the addition of lenalidomide and consolidation R-CHOP can be improved by adding fractionated anti-CD22 radioimmunotherapy (RIT) using 90Y-epratuzumab tetraxetan. Annalisa Chiappella (Turin, Italy) and coworkers found adding lenalidomide to R-CHOP21 resulted in an 86% complete remission rate (42/49 patients) and an overall objective response rate of 92% (45/49). Meanwhile, Françoise
Kraeber-Bodere (Nantes, France) and colleagues found use of RIT with R-CHOP14 as a consolidation therapy resulted in an 81·9% complete remission rate (50/61 patients) and an overall objective response rate of 91·8% (56/61).
Bendamustine and lymphoma An international, open label, randomised phase 3 trial has shown bendamustine plus rituximab is non-inferior to R-CHOP21 or R-CVP for first-line treatment of advanced indolent nonHodgkin’s lymphoma or mantle-cell lymphoma. Ian Flinn (Nashville, TN, USA) indicated that 447 patients were randomised to either standard therapy (R-CHOP21 or R-CVP) or to six to eight cycles of bendamustine plus rituximab. Complete response rates for the entire patient population were the same in both treatment groups, meeting the statistical conditions of non-inferiority (p=0·0084). Patients with mantle-cell lymphoma were found to have superior complete response rates (p=0·018) when treated with the bendamustinecontaining regimen. Both regimens had distinctive adverse events with specific differences in the rates of nausea, alopecia, and haematological toxicities.
Targeting innate and adaptive immunity The humanised anti-PD1 monoclonal antibody pidilizumab has been shown to be active in combination with rituximab in follicular lymphoma, according to results of a phase 2 study presented by Jason Westin (Houston, TX, USA). 29 evaluable patients with relapsed follicular lymphoma who had received prior rituximab were found to respond well to the combination treatment. 66% (19/29 patients) had an objective response, and 52% (15/29) showed a complete response. This degree of efficacy compares well with historical data.
David Collingridge
www.thelancet.com/oncology Vol 14 February 2013
54th ASH Annual Meeting
Steve Gschmeissner/Science Photo Library
New IMiD for multiple myeloma
Published Online December 21, 2012 http://dx.doi.org/10.1016/ S1470-2045(12)70578-8 The annual meeting of the American Society of Hematology was held in Atlanta, GA, USA, on Dec 8–11, 2012
Pomalidomide plus low-dose dexamethasone is an effective treatment for refractory multiple myeloma according to results of a phase 3 open-label randomised trial. Meletios Dimopoulos (Athens, Greece) and colleagues found patients refractory to bortezomib, thalidomide, or lenalidomide treated with pomalidomide plus dexamethasone had a significant improvement in progression-free survival (HR 0·45, p<0·001) and overall survival (HR 0·53, p<0·001) compared with patients treated with high-dose dexamethasone alone. Further support for pomalidomide was also shown by Tomer Mark (New York, NY, USA) and colleagues, who reported good efficacy in a phase 2 trial of patients with heavily pretreated multiple myeloma using a combination of pomalidomide, dexamethasone, and clarithromycin, and by Jatin Shah (Houston, TX, USA) and colleagues who showed good responses in a phase 1/2 trial combining this particular IMiD with carfilzomib in relapsed/refractory with multiple myeloma.
Arsenic for APL The first head-to-head phase 3 trial of ATRA plus arsenic trioxide versus ATRA plus idarubicin has been done in patients with newly diagnosed acute promyelocytic leukaemia in hospitals in Italy and Germany. Francesco Lo-Coco (Rome, Italy) and colleagues found arsenic trioxide was non-inferior to chemotherapy in this setting and had a more tolerable toxicity profile. 2-year event-free survival was 97% vs 86·7% (p=0·03) for the arsenic trioxide regimen versus standard chemotherapy, respectively.
FLT3-directed therapy A multinational group lead by Jorge Cortes (Houston, TX, USA) have found the FLT3 tyrosine kinase inhibitor, quizartinib causes the highest singleagent responses seen to date in 112
relapsed or refractory patients with acute myeloid leukaemia. Responses were seen in both patients older than 60 years (N=134; composite complete remission of 54% for FLT3-IAD+ patients, 32% for FLT3-IAD– patients) and in patients who had failed secondline salvage chemotherapy or stem-cell transplantation (N=137; composite complete remission of 44% for FLT3-AD+ patients, 34% for FLT3-IAD– patients). Although drug doses were different for male and female patients, adverse events were manageable and could be mitigated with dose modifications.
No role for radiotherapy Results of a phase 3 non-inferiority trial (John Radford, Manchester, UK, and collegaues) have shown patients with early stage Hodgkin’s lymphoma with a negative PET scan after three cycles of ABVD have a good prognosis and do not require further treatment with involved field radiotherapy (IFRT). After ABVD therapy, researchers randomised PET-negative patients to either IFRT or no further treatment, and PET-positive patients to an additional cycle of ABVD and IFRT. All PET scans were reviewed centrally. 3-year overall survival was 97·0%, 99·5%, and 93·9%, respectively, for the three groups.
New options for DLBCL Up to 40% of elderly patients with diffuse B-cell lymphoma relapse after treatment with R-CHOP. Two phase 2 trials done in Europe have shown the efficacy of induction R-CHOP can be improved by the addition of lenalidomide and consolidation R-CHOP can be improved by adding fractionated anti-CD22 radioimmunotherapy (RIT) using 90Y-epratuzumab tetraxetan. Annalisa Chiappella (Turin, Italy) and coworkers found adding lenalidomide to R-CHOP21 resulted in an 86% complete remission rate (42/49 patients) and an overall objective response rate of 92% (45/49). Meanwhile, Françoise
Kraeber-Bodere (Nantes, France) and colleagues found use of RIT with R-CHOP14 as a consolidation therapy resulted in an 81·9% complete remission rate (50/61 patients) and an overall objective response rate of 91·8% (56/61).
Bendamustine and lymphoma An international, open label, randomised phase 3 trial has shown bendamustine plus rituximab is non-inferior to R-CHOP21 or R-CVP for first-line treatment of advanced indolent nonHodgkin’s lymphoma or mantle-cell lymphoma. Ian Flinn (Nashville, TN, USA) indicated that 447 patients were randomised to either standard therapy (R-CHOP21 or R-CVP) or to six to eight cycles of bendamustine plus rituximab. Complete response rates for the entire patient population were the same in both treatment groups, meeting the statistical conditions of non-inferiority (p=0·0084). Patients with mantle-cell lymphoma were found to have superior complete response rates (p=0·018) when treated with the bendamustinecontaining regimen. Both regimens had distinctive adverse events with specific differences in the rates of nausea, alopecia, and haematological toxicities.
Targeting innate and adaptive immunity The humanised anti-PD1 monoclonal antibody pidilizumab has been shown to be active in combination with rituximab in follicular lymphoma, according to results of a phase 2 study presented by Jason Westin (Houston, TX, USA). 29 evaluable patients with relapsed follicular lymphoma who had received prior rituximab were found to respond well to the combination treatment. 66% (19/29 patients) had an objective response, and 52% (15/29) showed a complete response. This degree of efficacy compares well with historical data.
David Collingridge
www.thelancet.com/oncology Vol 14 February 2013