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Most patients had intermediate-risk disease ( 73 %; per European Leukemia- Net criteria ).
Study investigators randomized participants to the following arms :
• Dauno90 : cytarabine 100 mg / m 2 for 7 days plus daunorubicin 90 mg / m 2 on days 3-5 ( n = 157 )
• Dauno60 : cytarabine 100 mg / m 2 for 7 days plus daunorubicin 60 mg / m 2 on days 3-5 ( n = 157 )
Bone marrow response was assessed at 15 days following initiation of chemotherapy . A “ good ” treatment response was defined as a blast count < 5 percent .
There was no statistically significant difference in response rates between the Dauno90 and Dauno60 groups : 47.8 % ( 95 % CI 39.7-55.9 ) vs . 42.7 % ( 95 % CI 34.8-50.8 ; p = 0.29 ).
“ The tolerability was similar in both dose levels with no obvious signs of excess toxicity ,” the authors noted , with similar proportions of patients in each group experiencing adverse events ( AEs ): 89.8 % in the 90 mg / m 2 group and 86.6 % in the 60 mg / m 2 .
A higher proportion of patients experienced grade ≥3 AEs in the 90 mg / m 2 group than the 60 mg / m 2 group ( 20.3 % vs . 16.2 %). Similarly , a slightly higher proportion in the former group experienced early mortality within 14 days following induction ( 1.3 % vs . 0.6 %), as well as at 28 days of treatment ( 3.2 % vs . 1.3 %; p = 0.251 ).
“ Apart from early response , we will now have to look at other relevant clinical outcomes of the trial , such as comparison of complete response rates , relapse-free survival , and overall survival , between the two treatment arms ,” Dr . Röllig explained . “ These findings need longer follow-up to be confirmed , but we hope to be able to show more mature results later this year .” Participants who achieved a good response in this study became eligible for a subsequent , ongoing randomized study , which is evaluating a second 7 + 3 induction .
In addition to the short followup , the study has not yet assessed more clinically meaningful endpoints , such as overall survival .
REFERENCE
Röllig C , Steffen B , Herbst R , et al . Randomized comparison of 90 mg versus 60 mg daunorubicin in 7 + 3 standard induction for newly diagnosed acute myeloid leukemia : results from the SAL-DaunoDouble trial . Abstract # S861 . Presented at the 23rd Congress of the European Hematology Association , June 16 , 2018 ; Stockholm , Sweden .
CheckMate 205 : Evaluating Nivolumab in Newly Diagnosed Hodgkin Lymphoma
In a study presented by Radhakrishnan Ramchandren , MD , at the 23rd Congress of the European Hematology Association , the four-drug regimen of nivolumab plus doxorubicin , vinblastine , and dacarbazine ( AVD ) was a safe therapeutic combination in patients with newly diagnosed , advancedstage classical Hodgkin lymphoma ( HL ).
Although frontline , multi-agent chemotherapy cures most newly diagnosed patients , “ those with advanced-stage classical HL have suboptimal outcomes and the high toxicity
BESPONSA™ ( inotuzumab ozogamicin ) is indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia ( ALL )
AIM FOR DEEP
REMISSION
Deep remission refers to MRD-negative remission , defined in the INO-VATE ALL study as leukemic cells comprising < 1 x 10 -4 of bone marrow nucleated cells per flow cytometry . 1
IMPORTANT SAFETY INFORMATION
WARNING : HEPATOTOXICITY , INCLUDING HEPATIC VENO-OCCLUSIVE DISEASE ( VOD ) ( ALSO KNOWN AS SINUSOIDAL OBSTRUCTION SYNDROME ) and INCREASED RISK OF POST – HEMATOPOIETIC STEM CELL TRANSPLANT ( HSCT ) NON-RELAPSE MORTALITY ( NRM ):
• Hepatotoxicity , including fatal and life-threatening VOD , occurred in patients who received BESPONSA . The risk of VOD was greater in patients who underwent HSCT after BESPONSA treatment . The use of HSCT conditioning regimens containing 2 alkylating agents and last total bilirubin ≥ upper limit of normal ( ULN ) before HSCT were significantly associated with an increased risk of VOD
• Other risk factors for VOD in patients treated with BESPONSA included ongoing or prior liver disease , prior HSCT , increased age , later salvage lines , and a greater number of BESPONSA treatment cycles
• Elevation of liver tests may require dosing interruption , dose reduction , or permanent discontinuation of BESPONSA . Permanently discontinue treatment if VOD occurs . If severe VOD occurs , treat according to standard medical practice
• There was a higher post-HSCT non-relapse mortality rate in patients receiving BESPONSA , resulting in a higher Day 100 post-HSCT mortality rate
Hepatotoxicity , Including Hepatic VOD : Hepatotoxicity , including fatal and life-threatening VOD , occurred in 23 / 164 patients ( 14 %) during or following treatment with BESPONSA or following subsequent HSCT . VOD was reported up to 56 days after the last dose during treatment or follow-up without an intervening HSCT . The median time from HSCT to onset of VOD was 15 days .
Patients with prior VOD or serious ongoing liver disease are at an increased risk of worsening liver disease , including development of VOD , following of intensive regimens limits their use in older or frail patients ,” Dr . Ramchandren , of the Barbara Ann Karmanos Cancer Institute at Wayne State University in Detroit , and colleagues noted . The anti-PD-1 immune checkpoint inhibitor nivolumab has demonstrated
The efficacy of BESPONSA was established on the basis of CR ( 35.8 % [ 39 / 109 ; 95 % CI , 26.8-45.5 ] with BESPONSA vs 17.4 % [ 19 / 109 ; 95 % CI , 10.8-25.9 ] with SC ), the duration of CR ( 8.0 months [ 95 % CI , 4.9-10.4 ] with BESPONSA vs 4.9 months [ 95 % CI , 2.9-7.2 ] with SC ), and the proportion of MRD-negative CR ( 89.7 % [ 35 / 39 ; 95 % CI , 75.8-97.1 ] with BESPONSA vs 31.6 % [ 6 / 19 ; 95 % CI , 12.6-56.6 ] with SC ) in the first 218 randomized patients . 1
treatment with BESPONSA . Monitor closely for signs and symptoms of VOD ; these may include elevations in total bilirubin , hepatomegaly ( which may be painful ), rapid weight gain , and ascites . For patients proceeding to HSCT , the recommended duration of treatment with BESPONSA is 2 cycles . A third cycle may be considered for patients who do not achieve a CR or CRi and MRD-negativity after 2 cycles . Monitor liver tests closely during the first month post HSCT , then less frequently thereafter , according to standard medical practice .
Grade 3 / 4 increases in aspartate aminotransferase , alanine aminotransferase , and total bilirubin occurred in 7 / 160 ( 4 %), 7 / 161 ( 4 %), and 8 / 161 ( 5 %) patients , respectively .
Increased Risk of Post-HSCT Non-Relapse Mortality ( NRM ): There was a higher post-HSCT NRM rate in patients receiving BESPONSA , resulting in a higher Day 100 post-HSCT mortality rate . The rate of post-HSCT NRM was 31 / 79 ( 39 %) with BESPONSA and 8 / 35 ( 23 %) with investigator ’ s choice of chemotherapy . In the BESPONSA arm , the most common causes of post- HSCT NRM included VOD and infections . Monitor closely for toxicities post HSCT , including signs and symptoms of infection and VOD .
Myelosuppression : Myelosuppression , and severe , life-threatening , and fatal complications of myelosuppression , including hemorrhagic events and infections , have occurred with BESPONSA . Thrombocytopenia and neutropenia were reported in 83 / 164 patients ( 51 %) and 81 / 164 patients ( 49 %), respectively . Febrile neutropenia was reported in 43 / 164 patients ( 26 %).
Monitor complete blood counts prior to each dose of BESPONSA and monitor for signs and symptoms of infection , bleeding / hemorrhage , or other effects of myelosuppression during treatment and provide appropriate management . As appropriate , administer prophylactic anti-infectives during and after treatment with BESPONSA . Dose interruption , dose reduction , or permanent discontinuation may be required .
38 ASH Clinical News