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52nd ASH annual meeting
News
52nd ASH annual meeting The 52nd annual meeting of the American Society of Hematology was held on Dec 4–7, 2010, in Orlando, FL, USA
Rituximab in FL Upfront rituximab significantly delays time to initiation of new treatment compared with watchful waiting for patients with asymptomatic follicular lymphoma (FL). 462 adult patients with stage II–IV asymptomatic FL were randomly assigned to either watchful waiting (A), upfront rituximab every week for 4 weeks (B), or B plus maintenance rituximab every 2 months for 2 years (C). Group B was stopped due to slow accrual and because a benefit for maintenance therapy was becoming apparent. The median time to initiation of new treatment, the primary endpoint, was 33 months for watchful waiting versus not reached in the rituximab groups. 48% of patients in group A were not receiving new treatment at 3 years versus 80% and 91% in groups B and C. Serious adverse events (SAEs) included infection, allergic reactions, and severe neutropenia. Presenter Kirit Ardeshna (London, UK) said patients on rituximab maintenance still respond to the drug later as primary therapy and that quality-of-life data, due next year, will be important in determining the use of upfront rituximab.
Brentuximab vedotin Patients with refractory or relapsed systemic anaplastic large-cell lymphoma (sALCL) had an overall response rate (ORR) of 87% (n=26; 17 complete, nine partial responses) to the CD30targeting agent brentuximab vedotin (SGN-35), according to interim findings of the first 30 patients in a phase 2 study reported by Andrei Shustov (Seattle, WA, USA). The population was heavily pretreated; median number of previous chemotherapy lines was two (range 1–6); 19 patients had primary refractory disease and 16 had not responded to their last treatment. Responses were durable (4–36 weeks), and 18 patients are still responding. Tumour burden was reduced in 97% of patients. Nausea, diarrhoea, and peripheral neuropathy were the main 18
side-effects. In another phase 2 study of 102 patients with relapsed or refractory heavily pretreated Hodgkin’s lymphoma, Robert Chen (Duarte, CA, USA) reported an ORR (the primary endpoint) of 75% in those given the antibody–drug conjugate, with a similar toxicity profile to that seen in sALCL.
Ponatinib and refractory CML Ponatinib, an oral pan-BCR-ABL inhibitor, is active in patients with refractory chronic myeloid leukaemia (CML), including those with the gatekeeper T351I mutation. Jorge Cortes (Houston, TX, USA) reported a phase 1 study in patients with refractory haematological malignancies. 13 of 60 Philadelphia chromosome-positive patients had a major molecular response, including six of 15 patients with T351I mutations. The most common drug-related AEs of any grade were thrombocytopenia (24%), headache (14%), and nausea (14%).
MM-015 trial Patients with newly diagnosed multiple myeloma (MM) respond better to continuous lenalidomide treatment than those who did not receive maintenance lenalidomide, Antonio Palumbo (Torino, Italy) reported. 459 transplant-ineligible patients were randomly assigned to receive melphalan, prednisone, and lenalidomide induction treatment plus lenalidomide maintenance (MPR-R), or fixed durations of melphalan and prednisone (MP), or MPR without maintenance lenalidomide. ORR for the primary comparison of MPR-R with MP was 77% versus 50% (p<0·001). Responses on MPR-R were also more rapid (median 2 vs 3 months; p<0·001) and the risk of progression lower (HR 0·423; p<0·001, 2-year progression-free survival [PFS] 55% vs 16%). However, grade 3 or 4 neutropenia was higher with MPR-R than it was with MP (71% vs 30%), as were thrombocytopenia (38% vs 14%)
and anaemia (24% vs 17%). Palumbo commented that MPR-R should be considered a new standard treatment option, especially for those aged 65–75 years, but might be too toxic for patients older than 75 years.
Additional bortezomib in FL Patients with relapsed or refractory FL given additional bortezomib have significantly improved PFS. 676 patients were randomly assigned to receive five cycles of bortezomib plus rituximab (BR) or rituximab alone (R). A third of patients had received three or more previous therapies and 44% had received previous rituximab. Median PFS, the primary endpoint, was 334 days (95% CI 278–365) for those on R alone versus 389 days (351–456) for the combination; HR 0·822 (95% CI 0·681–0·991). The ORR was also better for BR (49% vs 63%), although at the expense of more toxicity (grade 3 or worse 21% vs 46%). Peripheral neuropathy occurred in 17% of patients in the BR arm compared with 1% for R alone, but presenter Bertrand Coiffier (Lyon, France) noted this was mostly reversible on stopping treatment.
VMPT-VT versus VMP The four-drug combination of VMPT (bortezomib, melphalan, prednisone, and thalidomide) followed by VT maintenance is more active than VMP alone as initial treatment in 511 elderly patients with newly diagnosed MM, Antonio Palumbo reported. After a median follow-up of 26·1 months, 3-year PFS was 55% versus 38% in favour of the more intensive treatment (HR 0·65, 95% CI 0·49–0·85; p=0·002). Both the bortezomib administration schedule and induction treatment length were altered by protocol amendment in March, 2007, to reduce toxicities such as peripheral neuropathy and neutropenia.
Emma Grainger www.thelancet.com/oncology Vol 12 January 2011
52nd ASH annual meeting The 52nd annual meeting of the American Society of Hematology was held on Dec 4–7, 2010, in Orlando, FL, USA
Rituximab in FL Upfront rituximab significantly delays time to initiation of new treatment compared with watchful waiting for patients with asymptomatic follicular lymphoma (FL). 462 adult patients with stage II–IV asymptomatic FL were randomly assigned to either watchful waiting (A), upfront rituximab every week for 4 weeks (B), or B plus maintenance rituximab every 2 months for 2 years (C). Group B was stopped due to slow accrual and because a benefit for maintenance therapy was becoming apparent. The median time to initiation of new treatment, the primary endpoint, was 33 months for watchful waiting versus not reached in the rituximab groups. 48% of patients in group A were not receiving new treatment at 3 years versus 80% and 91% in groups B and C. Serious adverse events (SAEs) included infection, allergic reactions, and severe neutropenia. Presenter Kirit Ardeshna (London, UK) said patients on rituximab maintenance still respond to the drug later as primary therapy and that quality-of-life data, due next year, will be important in determining the use of upfront rituximab.
Brentuximab vedotin Patients with refractory or relapsed systemic anaplastic large-cell lymphoma (sALCL) had an overall response rate (ORR) of 87% (n=26; 17 complete, nine partial responses) to the CD30targeting agent brentuximab vedotin (SGN-35), according to interim findings of the first 30 patients in a phase 2 study reported by Andrei Shustov (Seattle, WA, USA). The population was heavily pretreated; median number of previous chemotherapy lines was two (range 1–6); 19 patients had primary refractory disease and 16 had not responded to their last treatment. Responses were durable (4–36 weeks), and 18 patients are still responding. Tumour burden was reduced in 97% of patients. Nausea, diarrhoea, and peripheral neuropathy were the main 18
side-effects. In another phase 2 study of 102 patients with relapsed or refractory heavily pretreated Hodgkin’s lymphoma, Robert Chen (Duarte, CA, USA) reported an ORR (the primary endpoint) of 75% in those given the antibody–drug conjugate, with a similar toxicity profile to that seen in sALCL.
Ponatinib and refractory CML Ponatinib, an oral pan-BCR-ABL inhibitor, is active in patients with refractory chronic myeloid leukaemia (CML), including those with the gatekeeper T351I mutation. Jorge Cortes (Houston, TX, USA) reported a phase 1 study in patients with refractory haematological malignancies. 13 of 60 Philadelphia chromosome-positive patients had a major molecular response, including six of 15 patients with T351I mutations. The most common drug-related AEs of any grade were thrombocytopenia (24%), headache (14%), and nausea (14%).
MM-015 trial Patients with newly diagnosed multiple myeloma (MM) respond better to continuous lenalidomide treatment than those who did not receive maintenance lenalidomide, Antonio Palumbo (Torino, Italy) reported. 459 transplant-ineligible patients were randomly assigned to receive melphalan, prednisone, and lenalidomide induction treatment plus lenalidomide maintenance (MPR-R), or fixed durations of melphalan and prednisone (MP), or MPR without maintenance lenalidomide. ORR for the primary comparison of MPR-R with MP was 77% versus 50% (p<0·001). Responses on MPR-R were also more rapid (median 2 vs 3 months; p<0·001) and the risk of progression lower (HR 0·423; p<0·001, 2-year progression-free survival [PFS] 55% vs 16%). However, grade 3 or 4 neutropenia was higher with MPR-R than it was with MP (71% vs 30%), as were thrombocytopenia (38% vs 14%)
and anaemia (24% vs 17%). Palumbo commented that MPR-R should be considered a new standard treatment option, especially for those aged 65–75 years, but might be too toxic for patients older than 75 years.
Additional bortezomib in FL Patients with relapsed or refractory FL given additional bortezomib have significantly improved PFS. 676 patients were randomly assigned to receive five cycles of bortezomib plus rituximab (BR) or rituximab alone (R). A third of patients had received three or more previous therapies and 44% had received previous rituximab. Median PFS, the primary endpoint, was 334 days (95% CI 278–365) for those on R alone versus 389 days (351–456) for the combination; HR 0·822 (95% CI 0·681–0·991). The ORR was also better for BR (49% vs 63%), although at the expense of more toxicity (grade 3 or worse 21% vs 46%). Peripheral neuropathy occurred in 17% of patients in the BR arm compared with 1% for R alone, but presenter Bertrand Coiffier (Lyon, France) noted this was mostly reversible on stopping treatment.
VMPT-VT versus VMP The four-drug combination of VMPT (bortezomib, melphalan, prednisone, and thalidomide) followed by VT maintenance is more active than VMP alone as initial treatment in 511 elderly patients with newly diagnosed MM, Antonio Palumbo reported. After a median follow-up of 26·1 months, 3-year PFS was 55% versus 38% in favour of the more intensive treatment (HR 0·65, 95% CI 0·49–0·85; p=0·002). Both the bortezomib administration schedule and induction treatment length were altered by protocol amendment in March, 2007, to reduce toxicities such as peripheral neuropathy and neutropenia.
Emma Grainger www.thelancet.com/oncology Vol 12 January 2011