Carfilzomib-Based Regimens Are Efficacious and Well Tolerated in Heavily Pre-Treated Multiple Myeloma Patients: Real World Data from a Norwegian Cohort
Authors: Lysén Anna , Haarstad Ina , Schjesvold Fredrik H. 
Published: October 2019

Abstract
Introduction
Multiple myeloma (MM) is considered an incurable disease. However, during the last years the survival has improved, partly due to the development of new drugs. The second-generation proteasome inhibitor Carfilzomib (Kyprolis®) was first approved for marketing in Norway in January 2016. Carfilzomib in combination with Dexamethasone (Kd) for patients with relapsing and/or refractory multiple myeloma (RRMM) was approved for reimbursement in August 2017, while the combination with Lenalidomide (Revlimid®) and Dexamethasone (KRd) is still not reimbursed in Norway. Both regimens now have mature and beneficial survival data (vs Vd and Rd, respectively). In the period before market approval, Carfilzomib was provided through a named patient program (NPP) for patients who had a critical disease with few treatments options. This abstract presents results from this cohort.
Aim
In this retrospective study all 33 Norwegian MM patients who received Carfilzomib through a named patient program (NPP) during the period of March 2014 to January 2016, were included. The aim was to describe the patients 'characteristics and their treatment responses, in addition to use the real-life experience to highlight a possible benefit of making new drugs available before marketing approval. During this study period, neither Daratumumab, Ixazomib nor Elotuzumab were available in Norway. The medical records were printed and sent from 10 different hospitals to Oslo Myeloma Center. Baseline values and treatment responses was assessed and entered into our myeloma database. Statistical analysis was done to determine response rates and time to event outcomes.
Results
The participants had received a median of 6 (1-11) previous lines of therapy, including bortezomib (100%), and thalidomide and/or lenalidomide (97%) before inclusion in this study Among these, 64 % or 66 % respectively was refractory to the indicated treatment. 76 % of the study participants had received at least one ASCT. Median time from diagnosis to initiating carfilzomib treatment was 5 years (0-15) for the 32 patients who received carfilzomib. Patients who received the triplet treatment KRd, had a benefit in terms of response with ORR of 19%, compared to 8 %for patients receiving Kd/K (p=0, 04). CBR for these patients was 22 % and 25 %, respectively (p=0,33). There was no difference between the two groups for PFS or OS, with a median OS of 10 months (0-24) for patients receiving KRd compared to 9 month (2-14) for Kd/K. However, patients receiving KRd showed a trend towards a better PFS compared to Kd with a median PFS of 3,5 months (1,4 - 4,6) compared to 2,5 months (0,2 - 3,8) (p=0,095).
Adverse events occurred in 91 % of the patients where 41 %, 31 % and 41 % respectively experienced a Grade 3 or higher for anemia, neutropenia or thrombocytopenia (according to CTCAE vs 4.0). 19 % experienced cardiovascular complications and 3% ended treatment due to them. Of these patients, 50 % had received doxorubicin at a previous treatment line and 17% received doxorubicin in combination with Carfilzomib. Overall, 9% of the patients discontinued the treatment due to adverse events while 6 % died before the end of the treatment. Carfilzomib was not considered a direct cause of death in any of these patients. At the end of the study (January 2018), 76 % of the participants were dead.
Conclusion
In this real-life study, RRMM patients who received lenalidomide in addition to carfilzomib and dexametason showed a superior response in comparison with patients who received carfilzomib and dexamethasone with an ORR of 19 % versus 8 %. There was no significant overall survival benefit, but a trend towards a better PFS for KRd compared to Kd/K. As an overall conclusion, this group of highly treated MM patients had a benefit from receiving Carfilzomib in combination with lenalidomide before marketing approval.

Disclosures
Schjesvold: Oncopeptides: Consultancy; Novartis: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Adaptive: Consultancy; Bayer: Consultancy; Bristol Myers Squibb: Consultancy; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Abbvie: Honoraria.