Literature Scan
Combination Ibrutinib , Carfilzomib , and Dexamethasone Is Promising for Relapsed / Refractory MM
In a phase I dose-finding study , two-thirds of patients with relapsed / refractory multiple myeloma ( MM ) responded to the triplet combination of ibrutinib plus carfilzomib and dexamethasone , according to results published in Leukemia & Lymphoma . Ajai Chari , MD , of the Tisch Cancer Institute at Mount Sinai in New York , and co-authors also reported that the combination had a “ manageable safety profile .”
The multicenter , open-label , phase I / IIb PCYC-1119 study enrolled 43 patients with MM ( median age = 63 years ; range = 44-83 years ) who had received two or more prior lines of therapy , including bortezomib and an immunomodulatory drug ( IMiD ). Patients were excluded from the trial if they were refractory or non-responsive to prior carfilzomib .
The median time from MM diagnosis to trial enrollment was 4.2 years ( range = 0.5-25.3 years ), and patients had received a median of three prior lines of therapy ( range = 2-9 therapies ). Most ( 70 %) had received a prior autologous hematopoietic cell transplantation . Participants were refractory to bortezomib ( 74 %), lenalidomide ( 72 %), and pomalidomide ( 28 %), and 60 percent were refractory to both a proteasome inhibitor and IMiD . Twenty-three percent of patients had high-risk cytogenetics , including 19 percent with t ( 4 ; 14 ), 9 percent with t ( 11 ; 14 ), and 7 percent with del17p mutation .
In a 3 + 3 dose-escalation design , participants were assigned to the following cohorts and treated with 28-day cycles of :
• ibrutinib 560 mg ; carfilzomib 27 mg / m 2 ; no dexamethasone ( cohort 1 , n = 3 )
• ibrutinib 560 mg ; carfilzomib 36 mg / m 2 ; no dexamethasone ( cohort 2a , n = 5 )
• ibrutinib 560 mg ; carfilzomib 36 mg / m 2 ; dexamethasone 20 mg ( cohort 2b , n = 17 )
• ibrutinib 840 mg ; carfilzomib 36 mg / m 2 ; dexamethasone 20 mg ( cohort 3b , n = 18 )
The first 13 patients completed the doselimiting toxicity ( DLT ) observation period , and an additional 30 patients were enrolled during the dose-expansion phase to cohorts 2b and 3b .
38 ASH Clinical News
All trial participants experienced at least one any-grade , treatment-related adverse event ( AE ), and 37 patients ( 86 %) experienced a grade ≥3 AE . The researchers
ADYNOVATE ® is FDA approved for patients of all ages with Hemophilia A
PROVEN PROPHYLAXIS + SIMPLE ,* TWICE-WEEKLY
DOSING SCHEDULE = moments
Y OSING SCHEDULE =
THEIR WAY
* ADYNOVATE allows patients to infuse on the same 2 days every week .
ADYNOVATE [ Antihemophilic Factor ( Recombinant ), PEGylated ] Important Information
Indications
ADYNOVATE , Antihemophilic Factor ( Recombinant ), PEGylated , is a human antihemophilic factor indicated in children and adults with hemophilia A ( congenital factor VIII deficiency ) for :
• On-demand treatment and control of bleeding episodes
• Perioperative management
• Routine prophylaxis to reduce the frequency of bleeding episodes
Limitation of Use ADYNOVATE is not indicated for the treatment of von Willebrand disease . observed no DLTs during the doseescalation phase , so the recommended phase II dose ( primary endpoint ) was ibrutinib 840 mg with carfilzomib 36 mg / m 2 and dexamethasone adjusted for age .
The most common hematologic AEs were anemia ( 35 %), thrombocytopenia ( 28 %), and neutropenia ( 9 %); the most
DETAILED IMPORTANT RISK INFORMATION
CONTRAINDICATIONS
ADYNOVATE is contraindicated in patients who have had prior anaphylactic reaction to ADYNOVATE , to the parent molecule ( ADVATE [ Antihemophilic Factor ( Recombinant )]), mouse or hamster protein , or excipients of ADYNOVATE ( e . g . Tris , mannitol , trehalose , glutathione , and / or polysorbate 80 ).
WARNINGS & PRECAUTIONS Hypersensitivity Reactions
Hypersensitivity reactions are possible with ADYNOVATE . Allergic-type hypersensitivity reactions , including anaphylaxis , have been reported with other recombinant antihemophilic factor VIII products , including the parent molecule , ADVATE . Early signs of hypersensitivity reactions that can progress to anaphylaxis may include angioedema , chest tightness , dyspnea , wheezing , urticaria , and pruritus . Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur .