Contributions
Type: Oral Presentation + travel grant
Presentation during EHA20: From 13.06.2015 12:00 to 13.06.2015 12:15
Location: Room A2+3
Background
Triplet regimens containing an immunomodulatory agent (IMiD), proteasome inhibitor (PI) or both, are standard induction therapy for myeloma (MM) patients. Attempts to improve responses with quadruplets containing bortezomib and lenalidomide led to increased toxicity without improving outcomes. New generation PIs such as carfilzomib, with less off-target activity and better toxicity profiles are now available and recent data from the ASPIRE trial demonstrate that the triplet carfilzomib, lenalidomide, dexamethasone is safe and effective at relapse. Therefore, it is important to define whether a quadruplet combining carfilzomib and lenalidomide at induction can improve outcomes whilst minimising additional toxicity.
The UK NCRI Myeloma XI trial is the first large, phase III study aiming to answer this question with the addition of the quadruplet carfilzomib, cyclophosphamide, lenalidomide and dexamethasone (KCRD) experimental arm to the transplant eligible (TE) pathway. Overall the trial seeks to establish the optimum induction and maintenance approaches for all newly diagnosed MM (NDMM) patients with almost 4000 recruited to date.
Aims
To assess the safety and tolerability of KCRD in TE, NDMM.
Methods
In 2013, the TE pathway of the NCRI Myeloma XI trial was amended to include an assessment of the quadruplet carfilzomib (20/36mg/m2 IV D1-2,8-9,15-16. 20mg/m2 only cycle 1 D1-2), cyclophosphamide (500mg PO D1,8), lenalidomide (25mg PO D1-21), dexamethasone (40mg PO D1-4,8-9,15-16). This up-front quadruplet is being compared to the sequential strategy of triplet IMiD combinations (with thalidomide or lenalidomide) followed by additional PI triplet therapy (with bortezomib) for those with a suboptimal response (
Results
Following informed consent 257 patients have commenced KCRD treatment to date. KCRD is well tolerated with patients completing a mean of 4.2 cycles (±1.17), median 4 (range 1-7) prior to transplant. Dose modifications have been required in 63% of KCRD patients (55% with modifications to carfilzomib, 38% to lenalidomide). Data for study drug-related toxicity in patients who have completed at least one cycle of KCRD show a low incidence of grade 2-4 neuropathy (sensory 1.2%, motor 4.4%), all grade infusion reactions (4.4%) and thrombo-embolism (5%). Grade 3-4 haem toxicities were: 14.5% neutropenia, 6.9% thrombocytopenia, 7.5% anaemia. There were few reported cases of cardiac or renal failure so we looked for ARs suggestive of these previously reported side effects, finding grade 3-4 dyspnoea in only 1.3%. Serious adverse events suspected to be due to trial medications have occurred in 41% of patients receiving KCRD with the majority due to infections or cytopenias.
Overall the toxicity profile is similar to that reported previously for patients receiving the CRD triplet, despite the addition of carfilzomib.
Summary
These results suggest that KCRD, an outpatient delivered 4-drug regimen combining second generation IMiD and PI drugs, is well-tolerated and safe in TE NDMM patients. With no significant additional toxicity over 3–drug combinations and a favourable profile when compared to other 4-drug regimens, KCRD represents a highly promising induction option. Longer follow-up is awaited to assess the efficacy and tolerability compared to a sequential IMiD/PI strategy.
Keyword(s): Immunomodulatory thalidomide analog, Induction chemotherapy, Myeloma, Proteasome inhibitor
Session topic: Multiple myeloma: Clinical studies 2
Type: Oral Presentation + travel grant
Presentation during EHA20: From 13.06.2015 12:00 to 13.06.2015 12:15
Location: Room A2+3
Background
Triplet regimens containing an immunomodulatory agent (IMiD), proteasome inhibitor (PI) or both, are standard induction therapy for myeloma (MM) patients. Attempts to improve responses with quadruplets containing bortezomib and lenalidomide led to increased toxicity without improving outcomes. New generation PIs such as carfilzomib, with less off-target activity and better toxicity profiles are now available and recent data from the ASPIRE trial demonstrate that the triplet carfilzomib, lenalidomide, dexamethasone is safe and effective at relapse. Therefore, it is important to define whether a quadruplet combining carfilzomib and lenalidomide at induction can improve outcomes whilst minimising additional toxicity.
The UK NCRI Myeloma XI trial is the first large, phase III study aiming to answer this question with the addition of the quadruplet carfilzomib, cyclophosphamide, lenalidomide and dexamethasone (KCRD) experimental arm to the transplant eligible (TE) pathway. Overall the trial seeks to establish the optimum induction and maintenance approaches for all newly diagnosed MM (NDMM) patients with almost 4000 recruited to date.
Aims
To assess the safety and tolerability of KCRD in TE, NDMM.
Methods
In 2013, the TE pathway of the NCRI Myeloma XI trial was amended to include an assessment of the quadruplet carfilzomib (20/36mg/m2 IV D1-2,8-9,15-16. 20mg/m2 only cycle 1 D1-2), cyclophosphamide (500mg PO D1,8), lenalidomide (25mg PO D1-21), dexamethasone (40mg PO D1-4,8-9,15-16). This up-front quadruplet is being compared to the sequential strategy of triplet IMiD combinations (with thalidomide or lenalidomide) followed by additional PI triplet therapy (with bortezomib) for those with a suboptimal response (
Results
Following informed consent 257 patients have commenced KCRD treatment to date. KCRD is well tolerated with patients completing a mean of 4.2 cycles (±1.17), median 4 (range 1-7) prior to transplant. Dose modifications have been required in 63% of KCRD patients (55% with modifications to carfilzomib, 38% to lenalidomide). Data for study drug-related toxicity in patients who have completed at least one cycle of KCRD show a low incidence of grade 2-4 neuropathy (sensory 1.2%, motor 4.4%), all grade infusion reactions (4.4%) and thrombo-embolism (5%). Grade 3-4 haem toxicities were: 14.5% neutropenia, 6.9% thrombocytopenia, 7.5% anaemia. There were few reported cases of cardiac or renal failure so we looked for ARs suggestive of these previously reported side effects, finding grade 3-4 dyspnoea in only 1.3%. Serious adverse events suspected to be due to trial medications have occurred in 41% of patients receiving KCRD with the majority due to infections or cytopenias.
Overall the toxicity profile is similar to that reported previously for patients receiving the CRD triplet, despite the addition of carfilzomib.
Summary
These results suggest that KCRD, an outpatient delivered 4-drug regimen combining second generation IMiD and PI drugs, is well-tolerated and safe in TE NDMM patients. With no significant additional toxicity over 3–drug combinations and a favourable profile when compared to other 4-drug regimens, KCRD represents a highly promising induction option. Longer follow-up is awaited to assess the efficacy and tolerability compared to a sequential IMiD/PI strategy.
Keyword(s): Immunomodulatory thalidomide analog, Induction chemotherapy, Myeloma, Proteasome inhibitor
Session topic: Multiple myeloma: Clinical studies 2