NNDR Salvage Biochemotherapy Regimens for Therapy-Refractory Leukemia and Lymphoma Patients: A Report from the Parker Hughes Cancer Center.
Authors: Uckun Faith M. , Sarquis Mireille , Lundell Kathleen , Morar Sandra , Larson Jan , Eddy Linda , Oazi Sanjive 
Published: October 2019

Abstract
We examined the activity of vinorelbine-based salvage biochemotherapy regimens NNDR-I (Vinorelbine [Navelbine] 25 mg/m2 d1, d8, Mitoxantrone [Novantrone] 10 mg/m2 d1, Dexamethasone [Decadron] 20 mg BID d1 through 7, Rituximab [Rituxan] 375 mg/m2 d1,8,15,29) and NNDR-II (Vinorelbine 25 mg/m2 d1, Mitoxantrone 10 mg/m2 d1, Dexamethasone 20 mg BID d1 through7, Rituximab 375 mg/m2 d1,8,15,22, Fludarabine 25 mg/m2 d1, d2, d3) in 26 patients with lymphohematopoietic malignancies, including 3 adult chronic myeloid leukemia (CML) patients in blast crisis, 2 adult chronic lymphocytic leukemia (CLL) patients with rapidly progressive leukemia, 10 acute lymphoblastic leukemia (ALL)(2 adults, 8 children) patients in therapy refractory relapse, and 11 adult non-Hodgkin’s lymhoma (NHL) patients (9 in relapse with progressive lymphoma). All patients completed their salvage therapy as an outpatient without infectious disease complications or hospitalizations. Of the 26 patients, 20 had objective responses, including 14 complete remissions (CR). The median survival was 1.3 (95% CI:0.5–3.9) y and the probability of survival was 53± 10% at 1 year and 37 ± 10% at 3 years (Figure 1). All 3 CML patients achieved a CR; two subsequently underwent allogeneic stem cell transplantation and remain alive free of leukemia at 4.5 y and 5.0 y, respectively, post blast crisis. One died with progressive disease at 0.7y. Both CLL patients achieved a CR and remain alive in CCR at 0.6y and 4.5y, respectively. Of the 10 ALL patients, 5 achieved a CR; of these 5, 2 died of pulmonary Aspergillosis at 0.3 y, 1 died of CMV pneumonitis at 0.7 y, 1 relapsed and died of gram negative sepsis at 1.2 y during reinduction, and 1 remains alive at 4.5 y in continued CR on maintenance chemotherapy. The median survival was 4 months. Of the 11 NHL patients, 4 achieved a CR and 5 achieved a PR. The median survival was 1.5y and 4 remain alive disease-free at 2.5y, 2.5y, 3.5y and 4.0y, respectively. Drug sensitivity profiling of primary tumor cells was performed in 14 patients: the vinorelbine sensitivity of the patients’ leukemia/lymphoma cells predicted their clinical response to the NNDR regimens. Of the 9 responders tested, 8 were vinorelbine sensitive at the primary tumor cell level. Of the 5 non-responders tested, only one was vinorelbine sensitive at the primary tumor cell level. Taken together, these findings demonstrate that patients with high risk/poor prognosis leukemias and lymphomas can achieve meaningful objective responses in an outpatient setting using vinorelbine-based salvage regimens. Future application if the drug sensitivity profiling of primary tumor cells might help tailor the NNDR regimens to those who are most likely to respond.
Figure 1. Treatment Outcome of Leukemia/Lymphoma Patients receiving NNDR I/II Therapy Figure 1. Treatment Outcome of Leukemia/Lymphoma Patients receiving NNDR I/II Therapy