Treatment Outcomes and Toxicity Profile of Kyprolis in Multiple Myeloma: A Single Institution Experience

Background: Survival outcomes of Multiple Myeloma (MM) patients have significantly increased with recent advances in treatment. In the past decade several agents have been FDA approved due to improvement in the progression-free survival (PFS). Kyprolis is an irreversible proteasome inhibitor (PI) that was first approved in 2012 for treatment of MM. The real-world use of Kyprolis in treatment of MM is important to assess.

Aim:

The primary objective of this study is to evaluate the real-world outcome in overall response rates (ORR) for MM patients treated with Kyprolis. This was a retrospective study at a single center site in the Northwell Health system, evaluating patients at the Monter Cancer Center. Secondary objectives include determining the PFS, and adverse side effects (ADEs), including cardiovascular and renal toxicities of MM patients treated with Kyprolis at our institution.

Methods:

We retrospectively analyzed the charts of patients with a known diagnosis of MM who were treated with Kyprolis between January 1, 2013, and December 31, 2018. Baseline patient demographics such as age, gender, MM stage at diagnosis based on the Revised International Staging System (R-ISS) criteria, cytogenetics and fluorescence in situ hybridization (FISH), prior treatment regimens, autologous stem cell transplant (ASCT) were collected. Statistical methods included percentage calculations of baseline characteristics. Time to progression was measured from start of treatment to disease progression. PFS was calculated as a mean from initiation of treatment to the time point when progression was first noticed.

Results:

We identified 66 patients who fit our criteria of inclusion in this study. The median age was 65 years (Range 48 to 84). Based on the R-ISS staging, 7 (10%) patients were stage I, 28 (42.4%) stage II, and 31 (47.0%) were stage III. Based on cytogenetics 31% of the patients were classified as high risk (defined as having a 13q deletion, t (4,14), del(17p), t (14,16), or gain 1q). There were 32.3% of the patients with hyperploidy. A subset of patients was heavily pretreated with approximately 18.2% receiving more than 4 treatment lines prior to initiation of Kyprolis and 22.7% having received 3 prior lines. 42.4% of patients received 2 prior lines of MM- directed therapy. Prior treatments mainly included immunomodulatory agents (IMiDs) such as Lenalidomide and Proteosome Inhibitors (PIs) such as Bortezomib. Cyclophosphamide in combination with Bortezomib and dexamethasone (CyBorD) was also a frequent pre-treatment regimen. In regards to ASCT, 42.4% of patients had undergone prior ASCT before Kyprolis therapy.

The overall response rate was 77.2%, with 6.2% having obtained a complete response (CR) as defined by the International Myeloma Working Group response criteria. Thirty-five (53%) patients terminated Kyprolis due to disease progression or intolerance and underwent a change in their treatment. There were 10 patients (15%) who required ASCT after receiving Kyprolis in the setting of progression of disease. The majority of patients that progressed received Daratumumab (40%) or Pomalidomide (46%). Regarding ADEs, grade 2 hypertension was noted in 14% of all patients, acute renal failure (ARF) in 17% of patients, dyspnea in 25.4%, gastrointestinal (GI) toxicity in 16.3%, and fatigue in 40.8% of patients who received Kyprolis. The median PFS on Kyprolis at this site was 6.96 months.

Conclusion:

Our study shows that Kyprolis improved PFS in patients with MM. However, these patients are at increased risk for cardiac and renal toxicity. This study varies from published findings of clinical trials. Our patients had a higher percentage of high-risk cytogenetics as compared to those in the ASPIRE trial. About 90% of patients in the ASPIRE study had an ECOG status of 0 or 1, which was better than the average seen in our patient population. These two factors may have contributed to a lower observed PFS than that initially observed in the clinical trials. Second, this is a retrospective single center study, with inherent biases that may result in additional variance.

The proportion of grade 2 ADEs were comparable to the frequencies reported in the ASPIRE and ENDEAVOR trials. The toxicities noted in this study reinforce the importance for community oncologists to be aware of these issues. Early prevention and management may impact quality of life, response, or tolerance to Kyprolis therapy.