Blood Cancer Treatment Advances Highlight Week in Cancer News
Top news of the week in oncology, and cancer drug development.
KTE-C19 Induces CRs in Phase 2 Lymphoma Study
Treatment with KTE-C19 demonstrated an objective response rate of 79% and a complete remission rate of 52% for patients with aggressive, chemorefractory non-Hodgkin's lymphoma, according to interim findings from the multicenter phase II ZUMA-1 study. The study included 51 patients with diffuse large B-cell lymphoma and 11 with either transformed follicular lymphoma or primary mediastinal B-cell lymphoma.
For those with DLBCL, the ORR with KTE-C19 was 76%, with a CR rate of 47%. In those with TFL/PMBCL, the ORR was 91% and the CR rate was 73%. Overall, 39% of patients with DLBCL treated with KTE-C19 experienced a response for at least 3 months and 33% had a CR for at least 3 months. For those with PMBCL/TFL, the 3-month ORR and CR rates were both 64%. Across the full study (n = 62), grade ≥3 cytokine release syndrome was experienced by 18% of patients, and 34% experienced grade ≥3 neurological toxicity.
There were 2 patient deaths related to KTE-C19-associated adverse events, specifically from hemophagocytic lymphohistiocytosis and cardiac arrest in a patient with CRS.
Carfilzomib Not Superior to Bortezomib in Phase 3 CLARION Study
Carfilzomib did not improve progression-free survival compared with bortezomib when used in combination with melphalan and prednisone as a treatment for transplant ineligible patients with newly diagnosed multiple myeloma, according to topline findings from the phase III CLARION study. Median PFS with carfilzomib, melphalan, and prednisone was 22.3 months compared with 22.1 months with bortezomib, melphalan, and prednisone (HR, 0.91; 95% CI, 0.75-1.10).
Additionally, the rate of fatal treatment-emergent adverse events was higher with carfilzomib versus bortezomib (6.5% vs 4.3%, respectively). An early assessment of overall survival also demonstrated a lack of superiority for carfilzomib versus bortezomib. At this assessment, the lower end of the confidence interval was 0.90 and the higher end was 1.64. The overall survival hazard ratio for carfilzomib versus bortezomib for was 1.21. Grade ≥3 adverse events were experienced by 74.7% of patients treated with carfilzomib compared with 76.2% with bortezomib.
Grade ≥2 peripheral neuropathy was experienced by 2.5% of patients treated with carfilzomib compared with 35.1% with bortezomib. The exact numbers for patients treated with IV versus SQ bortezomib were not yet released. Amgen released findings from the CLARION study. The company plans to submit full data for future presentation and publication.
Novel Agents Highlighted at NCCN Congress
The NCCN Annual Congress on Hematologic Malignancies took place this past weekend in New York. The congress focused on incorporating the latest agents into the treatment guidelines, along with new agents on the horizon. The most changes have taken place in the past year for the treatment of multiple myeloma. In the frontline setting, the preferred primary therapy for patients with multiple myeloma is induction therapy with a triplet regimen containing bortezomib, lenalidomide, and dexamethasone followed by autologous stem cell transplantation, consolidation, and maintenance lenalidomide.
In the second-line and beyond, the 4 most recently approved agents were recently incorporated into the guidelines, namely panobinostat, ixazomib, daratumumab, and elotuzumab. Overall, there have been 10 new agents approved for myeloma in the past 12 years.
Acute myeloid leukemia is another area about to undergo substantial upheaval. The treatment paradigm has traditionally be 7:3, but now several novel agents are moving through the pipeline. These include venetoclax (Venclexta), midostaurin, and CPX-351, all of which have received breakthrough therapy designations.
Adding RT to Chemo Improves PFS for Follicular Lymphoma
Chemoradiation for early-stage, low-grade follicular lymphoma led to significant improvement in progression-free survival compared with involved-field radiotherapy alone, according to findings from a multicenter randomized trial presented at the ASTRO meeting. Patients who received chemotherapy in addition to IFRT had a 10-year PFS of 59% versus 41% for patients treated with radiotherapy alone.
A trial protocol amendment allowing the addition of rituximab to chemotherapy had a substantial impact on the PFS benefit. Most patients in both arms had prolonged OS. Patients randomized to systemic therapy had numerically superior OS at 10 years (95% vs 86%). However, the difference did not achieve statistical significance (P = 0.40). Systemic therapy also had a major impact on the occurrence of high-grade histologic transformation. More than twice as many patients treated with IFRT alone had disease transformation to high-grade lymphoma (10 vs 4 in the group that received IFRT plus systemic therapy).
Intensity-Modulated RT Less Toxic for Gynecologic Malignancies
Patients with endometrial and cervical cancer reported significantly less acute gastrointestinal toxicity when treated with pelvic intensity-modulated radiation therapy as opposed to standard pelvic radiation therapy, according to findings from a randomized phase III trial reported at the 2016 ASTRO Meeting. As assessed by a validated questionnaire, patients had a significantly higher composite bowel score after a 5-week IMRT protocol.
The overall score was driven by a significantly higher score on the bowel-function component of the questionnaire, although patients randomized to IMRT also reported numerically less bowel bother. Genitourinary toxicity, a secondary outcome, also was reduced among patients treated with IMRT. Comparison of bowel summary mean scores showed a 5-point difference in favor of the IMRT arm, -18.6 versus -23.6 for patients randomized to conventional pelvic radiation therapy (P = 0.048). The bowel function mean score was -14.8 in the IMRT group and -21.0 in the conventionally treated group (P = 0.02). The mean bowel bother scores were -22.3 in the IMRT group and -26.1 in the conventional RT group (P = 0.19).