S872 Carfilzomib Lenalidomide Dexamethasone (Krd) With or Without Transplantation in Newly Diagnosed Myeloma (Forte Trial): Efficacy According to Risk Status

Abstract

Background: ENKTL account for more than 20% of the peripheral T-cell lymphoma in Asia. Patients with r/r ENKTL have a poor prognosis after failing an L-asparaginase based regimen, and the median overall survival is less than 6 months. The overexpression of PD-L1 induced by EBV infection is a potential mechanism for ENKTL to avert immune surveillance, and recent studies of PD-1 antibodies in pts with r/r ENKTL have demonstrated potential efficacy. Sintilimab, a fully human anti-PD-1 monoclonal antibody, has a safety profile consistent with other approved PD-1 antibodies and was approved for r/r classical Hodgkin lymphoma in China in 2018. Aims: This multicenter, single-arm, phase 2 study aims to validate the efficacy and safety of sintilimab monotherapy in patients with r/r EN-KTL in China. Methods: Patients with pathologically confirmed r/r ENKTL were enrolled. Sintilimab was given 200 mg IV Q3W, until PD, death, unacceptable toxicity, or withdrawal from the study. Treatment beyond PD is allowed. Tumor response evaluation was performed by both PET-CT and CT/MRI with contrast. The primary endpoint was objective response rate based on LUGANO 2014 criteria. Data cut-off date for this analysis was Feb 2, 2019. Results: From Aug 31, 2017 to Feb 7, 2018, a total of 28 patients were enrolled: 60.7% male and the median age was 37 (range: 19~65) yr. Sixty-eight percent of patients were stage IV and 89.3% were ECOG PS  1. All patients had failed an L-asparaginase based regimen, the median lines of previous therapy were 3 (range: 1~13), 78.6% patients received prior radiotherapy and 7.1% had failed HSCT. Median duration of therapy was 14.04 (range: 1.4~17.3) months and 19 patients are still receiving sintilimab. Sixty-eight percent (19/28, 95%CI: 47.6%~84.1%) of patients achieved response (CR+PR), including 4 pts who experienced PD prior to having a response. DCR was 85.7%, including 5 pts who experienced PD before SD or response. The 1-year OS rate was 82.1% and the median OS has not been reached. Most TRAEs were G1~2 (67.9%) and no patients discontinued treatment due to AEs. The most common TRAE was decreased lymphocyte count (46.4%) and 84.6% were grade 1~2. SAEs occurred in 21.4% of patients and none were related to sintilimab. No patients died from AEs. Summary/Conclusion: Sintilimab is effective and well tolerated in r/r ENKTL and could be a promising treatment option for these patients. Early disease progression observed by PET scan in this study could be pseudo-progression as it did not correlate with poor outcome, which warrants further investigation. NCT03228836

Clinical Applications and Future Directions of Minimal Residual Disease Testing in Multiple Myeloma

“…Conversely, reaching MRD negativity at a sensitivity of 10 −5 -10 −6 seemed to overcome the inferior outcome observed in high-risk vs. standard-risk patients (48,58). However, it should be noted that high-risk patients require highly intensive regimens in order to achieve a proper level of MRD negativity (47,52,55).…”

“…NTE NDMM in ≥PR after 6 VMP(52) or VTP(50) induction cycles MFC (10 −4 -10 −5 )Post-induction 30% 3-year PFS: 90% vs. NR Roussel et al(39) TE NDMM after 3 VRd + ASCT + 2 VRd cycles followed by lenalidomide maintenance ≥CR after ASCT (241) MFC (10 −4 -10 −5 ) +100 days after ASCT 64% 3-year TTP: 76% vs. 58%Ferrero et al (41) TE NDMM in ≥VGPR after ASCT (39) undergoing VTd consolidation ASO-PCR (10 −4 -10 −5 ) Longitudinal Post-ASCT: 23%, Post-consolidation: 57% 6-month post-consolidation: 72% Median PFS: 68 vs. 23 months Korthals et al (11) TE NDMM after 2-4 cycles of idarubicin-dexamethasone undergoing ASCT ASO-PCR (10 −4 -10 −5 ) Post-induction and post-ASCT (+3-6 months) Post-induction: 17% Post-ASCT: 21% NA Lahuerta et al (42) NDMM alive and with MRD data available at 9 months after treatment start (609) MFC (10 −4 -10 −5 ) 9 months after treatment start 43% Median PFS* 63 months vs. NA (11-29 months in the other response categories) Gu et al (43) TE NDMM (101) MFC (50 −4 -10 −5 ) Longitudinal Post-induction: 37% Post-ASCT: 66% 2-year post-ASCT: 78% Median TTP: NR vs. NR Korde et al…”

Hematopoietic stem cell transplantation for blood cancers in the era of precision medicine and immunotherapy

“…Both approaches produce deep remissions, with a majority of patients achieving an MRD‐negative state. A recent update of this study reported a higher rate of early recurrence in the group treated with KRd only (ie, nontransplantation) (23% vs 12% in the group who underwent transplantation) . Although the results of this study are immature and PFS and OS data are forthcoming, this interim analysis suggests that even with highly active induction regimens that can achieve an MRD‐negative disease state in a majority of patients, the incorporation of autoHCT continues to provide benefit.…”

Consolidation with carfilzomib, lenalidomide, and dexamethasone (KRd) following ASCT results in high rates of minimal residual disease negativity and improves bone metabolism, in the absence of bisphosphonates, among newly diagnosed patients with multiple myeloma

“…More recently, the larger phase 2 FORTE clinical trial evaluated the efficacy of the same treatment schedule. Among 158 patients, NDMM patients who received KRd induction-ASCT-KRd consolidation, the CR or better rate was 60%, and the MRD-negative rate by NGF was 58% 10 . In all these studies, KRd was administered as induction followed by HDM/ASCT and KRd consolidation.…”