A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia in solid tumors and hematologic malignancies

Abstract

Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy delays, dose reductions, and discontinuation. There is no FDA-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at 4 U.S. centers. The primary outcome was achievement of a romiplostim response [median on-romiplostim platelet count (Plt) ≥75x109/L and ≥30x109/L above baseline]. Secondary outcomes included time to Plt≥100x109/L and rates of the following: Plt<100x109/L, Plt<75x109/L, Plt<50x109/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare weekly dosing with intracycle/intermittent dosing. 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of 4 (range, 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays and 89% avoided platelet transfusions. Median per-patient Plt on romiplostim was significantly higher than baseline (116x109/L vs. 60x109/L, P<0.001). Bone marrow tumor invasion, prior pelvic irradiation, and prior temozolomide predicted romiplostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays (IRR 3.00, 95% CI 1.30-6.91, P=0.010) or bleeding (IRR 4.84, 95% CI 1.18-19.89, P=0.029). Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with bone marrow involvement. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients.

Figure 1.

Chemotherapy-induced thrombocytopenia (CIT) romiplostim treatment pathways. In the weekly romiplostim dosing pathway, romiplostim is administered weekly irrespective of treatment schedule. In the intracycle romiplostim dosing pathway, romiplostim is dosed on chemotherapy off-weeks, except for chemotherapy regimens employing regular treatment without off-weeks in which case romiplostim is administered every other week. Platelet counts are obtained weekly in both pathways.

Figure 2.

Median weekly platelet counts for patients on romiplostim chemotherapy-induced thrombocytopenia (CIT) treatment pathway. (A) Solid tumor patients (n=153). Error bars represent interquartile ranges. (B) Solid tumor patients with no predictors of romiplostim nonresponse (n=122, blue); solid tumor patients with predictors of romiplostim non-response (n=31, gray) including bone marrow (BM) invasion by tumor, prior pelvic irradiation, or prior temozolomide treatment; aggressive lymphoma patients (n=13, red); and myeloma patients (n=7, purple). Error bars omitted for figure clarity. PNR: predictors of romiplostim non-response (includes BM invasion by tumor, prior temozolomide exposure, or prior pelvic irradiation).

Figure 3.

Median weekly platelet counts for solid tumor patients receiving standard weekly romiplostim dosing (n=65, dark blue) versus intracycle romiplostim dosing (n=57, light blue). Patients with predictors of romiplostim non-response (bone marrow invasion, prior pelvic irradiation, or prior temozolomide) were excluded from this figure to emphasize the difference specifically attributable to dosing regimen. Error bars represent interquartile ranges.