KYPROLIS, Lenalidomide and Dexamethasone Reduced the Risk of Death by 21 Percent Versus Lenalidomide and Dexamethasone Alone in Patients With Relapsed or Refractory Multiple Myeloma

clinical trials for rare diseases

Results Support Early Use of KYPROLIS at First Relapse

PRNewswire/ —  Amgen (NASDAQ:AMGN) today announced that the Journal of Clinical Oncology published positive overall survival (OS) findings from the final analysis of the Phase 3 ASPIRE trial, which demonstrated that the addition of KYPROLIS® (carfilzomib) to lenalidomide and dexamethasone (KRd) reduced the risk of death by 21 percent versus lenalidomide and dexamethasone alone (Rd) and extended OS by 7.9 months in patients with relapsed or refractory multiple myeloma (median OS 48.3 months for KRd versus 40.4 months for Rd, HR = 0.79, 95 percent CI, 0.67 – 0.95; 1-sided p=0.0045). Notably, an OS improvement of 11.4 months was observed for patients at first relapse (47.3 versus 35.9 months [HR = 0.81, 95 percent CI, 0.62 – 1.06]), supporting early use of KRd.

“Results from the final analysis of the Phase 3 ASPIRE trial published today in the Journal of Clinical Oncology are significant, as they further validate carfilzomib, lenalidomide and dexamethasone as a standard of care regimen for patients with relapsed or refractory multiple myeloma,” said Keith Stewart , M.B., Ch.B., Mayo Clinic in Arizona and principal investigator of the ASPIRE trial. “Furthermore, these data showed that early use of carfilzomib, lenalidomide and dexamethasone at first relapse provided nearly one additional year of survival for patients regardless of prior treatment with bortezomib or transplant.”

“As seen in two different Phase 3 studies, KYPROLIS-based regimens are the first and only therapy combinations to demonstrate a significant overall survival advantage for patients with relapsed or refractory multiple myeloma versus recent standards of care,” said David M. Reese , M.D., senior vice president of Translational Sciences and Oncology at Amgen . “We look forward to continuing conversations with regulatory authorities in the U.S. and Europe to add these results to the KYPROLIS label.”

The safety data from ASPIRE was consistent with the known safety profile of KYPROLIS. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were diarrhea, anemia, neutropenia, fatigue, upper respiratory tract infection, pyrexia, cough, hypokalemia, thrombocytopenia, muscle spasms, pneumonia, nasopharyngitis, nausea, constipation, insomnia and bronchitis.

The final analysis of ASPIRE included subgroup analyses by prior lines of therapy, prior Velcade® (bortezomib) exposure at first relapse, and prior transplant at first relapse. Among these three groups, there was an 18 to 29 percent reduction in the risk of death for KRd versus Rd, consistent with findings in the overall population. Median OS was 11.4 months longer for KRd versus Rd in patients who had received one prior line of therapy and 6.5 months longer for patients with two or more prior lines (48.8 versus 42.3 months [HR = 0.79, 95 percent CI, 0.62 – 0.99]). Among patients who had received one prior line, median OS was improved by 12 months with KRd versus Rd in those with prior Velcade exposure (45.9 versus 33.9 months [HR = 0.82; 95 percent CI, 0.56 – 1.19]) and by 7.9 months in those without prior Velcade (48.3 versus 40.4 months [HR = 0.80, 95 percent CI, 0.55 – 1.17]). Median OS was also improved by 18.6 months with KRd versus Rd among patients with prior transplantation at first relapse (57.2 versus 38.6 months [HR = 0.71, 95 percent CI, 0.48 -1.05]).

The KRd regimen used in this trial is currently approved in the U.S., European Union and other countries based on primary analysis of progression-free survival (PFS) in the ASPIRE study. Amgen has submitted a supplemental New Drug Application to the U.S. Food and Drug Administration and a variation to the marketing application to the European Medicines Agency to include the OS data from ASPIRE in the product information for KYPROLIS.

About ASPIRE
The international, randomized Phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) trial evaluated KYPROLIS in combination with lenalidomide and dexamethasone, versus lenalidomide and dexamethasone alone, in patients with relapsed or refractory multiple myeloma following treatment with one to three prior regimens. The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death. Secondary endpoints included OS, overall response rate, duration of response, disease control rate, health-related quality of life and safety. Patients were randomized to receive KYPROLIS (20 mg/m2 on days 1 and 2 of cycle one, escalating to 27 mg/m2 on days 8, 9, 15 and 16 of cycle one and continuing on days 1, 2, 8, 9, 15 and 16 of subsequent cycles), in addition to a standard dosing schedule of lenalidomide (25 mg per day for 21 days on, seven days off) and low-dose dexamethasone (40 mg per week in four-week cycles), versus lenalidomide and low-dose dexamethasone alone. The study randomized 792 patients at sites in North America, Europe and Israel.

Patients treated with KRd reported improved global health status, with higher Global Health Status/Quality of Life (QoL) scores compared with Rd over 18 cycles of treatment (2-sided p<0.0001) measured with the EORTC QLQ-C30, an instrument validated in multiple myeloma.

Overall survival by Revised International Staging System (R-ISS) stage was also assessed. For R-ISS stage I (KRd, n = 42; Rd, n = 46), median OS was not reached for KRd and was 58 months for Rd (HR = 0.49, 95 percent CI, 0.26 – 0.92). For patients with R-ISS stage II (KRd, n = 194; Rd, n = 195), median OS was 45.4 months for KRd and 41.2 months for Rd (4.2 months; HR = 0.86, 95 percent CI, 0.68 – 1.10). For the small number of patients with R-ISS stage III (KRd, n = 37; Rd, n = 47), median OS was 23.3 months for KRd and 18.8 months for Rd (4.5 months; HR = 1.05, 95 percent CI, 0.66 – 1.68).

For the overall study population, treatment discontinuation due to an adverse event occurred in 19.9 percent of patients treated with KRd and 21.5 percent of patients receiving Rd. Fatal adverse events were reported in 11.5 percent of KRd-treated patients and 10.5 percent of patients treated with Rd. Grade =3 adverse event rates were 87 percent for KRd and 83 percent for Rd. Selected grade =3 adverse events of interest (grouped terms; KRd vs Rd) included acute renal failure (3.8 percent versus 3.3 percent), cardiac failure (4.3 percent versus 2.1 percent), and hypertension (6.4 percent versus 2.3 percent).

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.1 It is a rare and life-threatening disease that accounts for approximately one percent of all cancers. 2,3 Worldwide, approximately 114,000 people are diagnosed with multiple myeloma each year and 80,000 patient deaths are reported on an annual basis.2

About KYPROLIS® (carfilzomib) 
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.4 KYPROLIS has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.4 In some cells, KYPROLIS can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins. 4,5

KYPROLIS is approved in the U.S. for the following:

  • In combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
  • As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.

KYPROLIS is also approved in Argentina , Australia , Bahrain , Canada , Hong Kong , Israel , Japan , Kuwait , Lebanon , Macao , Mexico , Thailand , Colombia , S. Korea, Canada , Qatar , Switzerland , United Arab Emirates , Turkey , Russia , Brazil , India , Oman and the European Union . Additional regulatory applications for KYPROLIS are underway and have been submitted to health authorities worldwide.

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