Broad Range Of Kyprolis Studies Presented At ASH 2013
Published: Jan 28, 2014 7:12 pm
The 2013 annual meeting of the American Society of Hematology (ASH), which took place last month, featured many oral and poster presentations about Kyprolis, one of the newest drugs to be approved for the treatment of multiple myeloma.
The drug continues to be tested in various combinations in both newly diagnosed and relapsed/refractory multiple myeloma patients, as well as in patients with the myeloma precursor disease smoldering myeloma.
In most trials, Kyprolis (carfilzomib) was combined with dexamethasone (Decadron) and a third drug, sometimes even a fourth drug, such as Revlimid (lenalidomide), thalidomide (Thalomid), cyclophosphamide (Cytoxan), or clarithromycin (Biaxin).
Most of these combinations are ones in which Kyprolis replaced Velcade (bortezomib) in a regimen that has already been shown to be highly effective. Kyprolis and Velcade belong to the same class of drugs called proteasome inhibitors.
Across all different patient populations, Kyprolis continues to show strong results, with overall response rates ranging from 100 percent in smoldering multiple myeloma patients, to the 90 percent range in newly diagnosed (symptomatic) myeloma patients, and to the 60 to 70 percent range in relapsed patients.
Where comparisons can be made, Kyprolis-based combinations appear to have higher response rates, or deeper responses, than the equivalent Velcade-based combinations.
Kyprolis In Newly Diagnosed Myeloma Patients
Kyprolis-Revlimid-Dexamethasone Plus Revlimid Maintenance
Dr. Neha Korde from the National Cancer Institute and the National Institutes of Health presented updated results from a Phase 2 trial of Kyprolis, Revlimid, and dexamethasone followed by Revlimid maintenance therapy for newly diagnosed myeloma patients (abstract).
Among the 43 patients included in the study, 98 percent responded, with 51 percent achieving a stringent or complete response, 16 percent a near complete response, 21 percent a very good partial response, and 9 percent a partial response.
Among all the patients who reached at least a near complete response, 100 percent of those tested were negative for minimal residual disease.
The one-year progression-free survival rate was 97 percent.
Dr. Korde also reported that the regimen was an effective and tolerable regimen for older patients.
Comparisons to Velcade-Revlimid-dexamethasone for newly diagnosed myeloma are not simple, in that most studies of the Velcade-based regimen allowed patients to undergo stem cell transplantation or Velcade maintenance therapy, while patients in the Kyprolis study received Revlimid maintenance therapy.
The studies show that response rates are nearly 100 percent for both the Velcade- and Kyprolis three-drug regimens, with around 40 percent of patients receiving the Velcade-based regimen also undergoing stem cell transplantation.
However, two studies of the Velcade-based regimen show that 75 percent to 84 percent of patients treated with the regimen responded within four cycles, while the Kyprolis study showed that 98 percent responded in just two cycles.
Kyprolis-Cyclophosphamide-Dexamethasone Plus Kyprolis Maintenance
Dr. Sara Bringhen from the University of Torino in Italy reported results from a Phase 2 study evaluating Kyprolis, cyclophosphamide, and dexamethasone as initial therapy for older, newly diagnosed multiple myeloma patients (abstract; presentation [pdf] courtesy of Dr. Bringhen). After initial therapy, patients received further Kyprolis maintenance therapy.
Overall 96 percent of study participants responded, with 64 percent reaching a complete or near complete response, 12 percent a very good partial response, and 20 percent a partial response.
The two-year progression-free survival rate was 76 percent, and the overall survival rate was 87 percent.
According to Dr. Bringhen, Kyprolis-cyclophosphamide-dexamethasone therapy compares very favorably to other treatment options for older patients, both in terms of efficacy and safety.
Several previous studies have shown that the Velcade-based version of this induction therapy (commonly referred to as VCD or CyBorD) is highly effective for newly diagnosed myeloma patients. One study demonstrated the combination’s efficacy and safety specifically in older patients; however, the study did not include maintenance therapy. Given that response rates prior to maintenance therapy were not presented for the current study, it is difficult to make direct comparisons between the Kyprolis- and Velcade-based cyclophosphamide and dexamethasone regimens for older myeloma patients.
Kyprolis Plus Melphalan And Prednisone
Overall, 91 percent of patients responded, with 55 percent achieving at least a very good partial response. The median event-free survival was 22 months, and the two-year overall survival was 84 percent.
This combination appears to compare favorably to Velcade plus melphalan and prednisone for older newly diagnosed myeloma patients. A previous study showed that the overall response rate for this combination was 79 percent, with 47 percent achieving at least a very good partial response.
In addition, only 6 percent of patients treated with Kyprolis-melphalan-prednisone developed moderate or severe peripheral neuropathy (pain, tingling, or loss of sensation in the extremities), making it a safe and effective option for older patients. Similarly, 8 percent of patients treated in a previous study with the Velcade-based combination developed moderate to severe peripheral neuropathy.
Kyprolis Plus Cyclophosphamide, Thalidomide, And Dexamethasone
A poster presented at ASH summarized the final results of a Phase 1/2 study of Kyprolis plus cyclophosphamide, thalidomide, and dexamethasone – a combination therapy known as “CYCLONE” – in newly diagnosed myeloma patients (abstract).
According to the researchers, the combination is highly efficacious. After four treatment cycles, 91 percent of patients responded, with 76 percent achieving at least a very good partial response.
The two-year progression-free survival was 77 percent, and the two-year overall survival was 98 percent.
Kyprolis Plus Dexamethasone, Followed By Revlimid-Clarithromycin-Dexamethasone Consolidation and Revlimid Maintenance
Another poster summarized results of a study that investigated a sequential approach of upfront Kyprolis plus dexamethasone, followed by consolidation therapy with Revlimid, clarithromycin (Biaxin), and dexamethasone, and finally Revlimid maintenance as first-line therapy for newly diagnosed myeloma patients (abstract).
Overall, 83 percent of patients responded to Kyprolis-dexamethasone induction (9 percent stringent complete response, 39 percent very good partial response, and 35 percent partial response). According to the researchers, these response rates compare favorably to similar studies using Velcade-based combinations.
The researchers point out that responses deepened with consolidation and maintenance therapy (13 percent stringent complete response, 48 percent very good partial response, and 26 percent partial response for an overall response rate of 87 percent).
Kyprolis In Relapsed And Refractory Myeloma Patients
Weekly High-Dose Kyprolis
Results from a Phase 1 study of once-weekly (rather than twice-weekly), high-dose Kyprolis plus dexamethasone for relapsed or refractory myeloma were summarized in a poster presented at ASH (abstract).
Eighteen patients, with a median of one prior treatment regimen, have been enrolled and treated in the study thus far. The patients were given Kyprolis infusions once a week for three weeks out of each four-week cycle. After an initial starting dose of 20 mg/m2, patients subsequently received doses of Kyprolis ranging from 45 to 88 mg/m2.
Patients also were given 40 mg of dexamethasone once every week.
Thus far, two-thirds of the patients have achieved at least a partial response to the weekly high-dose Kyprolis and dexamethasone therapy. This compares favorably, the investigators note, to the 55 percent to 60 percent response rate seen in a separate study using twice-weekly Kyprolis.
The median time to response was one month, which the investigators described as rapid.
Kyprolis In Smoldering Myeloma Patients
Kyprolis-Revlimid-Dexamethasone Followed By Extended Revlimid
Another poster summarized results from a pilot study of Kyprolis in combination with Revlimid and dexamethasone followed by extended Revlimid dosing for high-risk smoldering myeloma (abstract; full poster [pdf] courtesy of Dr. Ola Landgren). Earlier results from the study were presented at the International Myeloma Workshop in April 2013 (see related Beacon news).
Among the 12 patients evaluated for response, all achieved at least a near complete response. In addition, 92 percent had no minimal residual disease detected.
For more information, please see the Beacon’s ASH 2013 Myeloma Gateway.
Tags: Multiple Myeloma, Carfilzomib, Kyprolis, ASH 2013 Meeting
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