Literature Scan
Evaluating Venetoclax Plus Daratumumab and Dexamethasone in Relapsed / Refractory MM
Treatment with oral BCL-2 inhibitor venetoclax induced deep and durable responses in patients with relapsed or refractory multiple myeloma ( MM ), especially those with t ( 11 ; 14 ) translocation , according to recent findings published in the Journal of Clinical Oncology .
This phase I study , led by Nizar J . Bahlis , MD , of Arnie Charbonneau Cancer Institute at the University of Calgary in Canada , enrolled 48 patients with relapsed or refractory MM . Patients with t ( 11 ; 14 ) translocation received venetoclax in combination with daratumumab and dexamethasone ( VenDd ), while cytogenetically unselected patients were treated with VenDd plus bortezomib ( VenDVd ). There were 24 patients in each of the two treatment groups .
Patients receiving VenDd had a median age of 63 years ( range = 51-76 ) and had received a median of 2.5 prior lines of therapy ( range = 1-8 ). Of the 24 patients in this group , 14 ( 58 %) had International Staging System ( ISS ) stage II or III disease .
In the VenDVd group , patients had a median age of 64 years ( range = 41-80 ) and had received a median of one prior line of therapy ( range = 1-3 ). ISS stage II or III disease was reported in 14 patients ( 58 %).
The primary endpoints of the study were expansion-phase dosing , safety , and overall response rate ( ORR ). Secondary endpoints included further safety analysis , progression-free survival ( PFS ), duration of response ( DOR ), and measurable residual disease ( MRD ) negativity .
At screening , FISH analysis was performed on CD138-enriched bone marrow aspirates to assess t ( 11 ; 14 ) and known prognostic cytogenetic markers in MM . High-risk cytogenetics was defined as the presence of t ( 4 ; 14 ), t ( 14 ; 16 ), or del ( 17p ).
Patients were initially treated with venetoclax 400 mg once daily . After one cycle , upon determination of acceptable safety , 11 patients receiving VenDd and nine patients receiving VenDVd were enrolled to receive venetoclax 800 mg once daily .
During the first two 28-day cycles of VenDd , daratumumab was administered weekly . For cycles 3 through 6 , daratumumab was given every two weeks , then every four weeks thereafter . Initially , daratumumab was administered intravenously ( IV ), but the study protocol was changed to subcutaneous ( SC ) daratumumab at 1,800 mg . Patients received dexamethasone at 40 mg weekly , with dose reductions to
20 mg allowed for individuals with low body weights and those age 75 or older . For the first dose , dexamethasone was administered IV , then either IV or orally for subsequent doses .
During cycles 1 through 8 , VenDVd was administered in 21-day cycles , followed by 28-day cycles thereafter . For the first three cycles , patients received daratumumab as above , then every three weeks during cycles 4 through 8 and every four weeks beyond . On days 1 , 2 , 4 , 5 , 8 , 9 , 11 , 12 , and 15 of cycles 1-3 and days 1 , 2 , 4 , 5 , 8 , 9 , 11 , and 12 of cycles 4-8 , patients received dexamethasone at 20 mg , then 40 mg in subsequent cycles . Patients were given bortezomib at 1.3 mg / m 2 SC or IV on days 1 , 4 , 8 , and 11 of cycles 1-8 .
Median follow-up was 21 months ( range = 19-30 ) for patients in the VenDd group and 21.5 months ( range = 19-26 ) for patients receiving VenDVd .
In the VenDd arm , the ORR was 96 % ( all very good partial response or better [ ≥VGPR ]). The ORR in patients treated with VenDVd was 92 %, with 79 % experiencing ≥VGPR ( see FIGURE A on page 47 ).
In both treatment groups , median PFS was not reached . At 18 months , the PFS rate was 90.5 % ( 95 %
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