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Modulation of chemosensitivity by alpha interferon in multiple myeloma and non-Hodgkin's lymphoma
R V Iaffaioli1, G Facchini, A Tortoriello
1Istituto di Medicina Interna, Universita di Cagliari, Italy.
Abstract:
Low-grade non-Hodgkin's lymphoma and multiple myeloma are chemosensitive malignancies, but are rarely curable because of primary or acquired drug resistance. Interferon has been shown to modulate the multidrug resistance phenotype and to reinduce chemosensitivity in patients with chemoresistant tumors. Fifteen patients with multiple myeloma and 64 patients with low/intermediate grade non-Hodgkin's lymphoma unresponsive to initial chemotherapy were treated with alpha 2b interferon for 2 months. In case of an objective response, treatment was continued until disease progression; non-responding patients received the same chemotherapy to which they were resistant, preceded by a 5 day course of interferon. Interferon salvage monotherapy induced an objective response in 1/15 patients with multiple myeloma and in 7/64 patients with non-Hodgkin's lymphoma. An objective response was achieved after retreatment with first-line chemotherapy preceded by interferon in 4/14 patients (28.6%) with multiple myeloma and in 20/56 evaluable patients (35.7%) with non-Hodgkin's lymphoma. Toxicity was moderate, predictable, manageable, and never caused interruption of the treatment. Interferon appears to be able to modulate chemosensitivity of tumors refractory to chemotherapy with several potential mechanisms, including an effect on drug accumulation; its utilization in this setting warrants further evaluation.
Insights
Interferon alpha 2b can re-sensitize chemotherapy-resistant non-Hodgkin's lymphoma and multiple myeloma. This approach showed moderate toxicity and warrants further investigation for refractory cancers.
Area of Science:
- Oncology
- Hematology
- Pharmacology
Background:
- Low-grade non-Hodgkin's lymphoma and multiple myeloma are often resistant to chemotherapy.
- Drug resistance limits curative treatment options for these hematologic malignancies.
Purpose of the Study:
- To evaluate the efficacy of interferon alpha 2b in re-inducing chemosensitivity in patients with refractory non-Hodgkin's lymphoma and multiple myeloma.
- To assess the safety and tolerability of interferon alpha 2b in this patient population.
Main Methods:
- A total of 15 multiple myeloma and 64 non-Hodgkin's lymphoma patients received 2 months of interferon alpha 2b.
- Non-responding patients were retreated with prior chemotherapy preceded by a 5-day interferon course.
- Objective response rates and toxicity were monitored.
Main Results:
- Interferon monotherapy yielded objective responses in 1/15 multiple myeloma and 7/64 non-Hodgkin's lymphoma patients.
- Chemotherapy preceded by interferon resulted in objective responses in 28.6% of multiple myeloma and 35.7% of non-Hodgkin's lymphoma patients.
- Observed toxicity was manageable and did not necessitate treatment interruption.
Conclusions:
- Interferon alpha 2b can modulate tumor chemosensitivity in patients with refractory hematologic malignancies.
- Interferon salvage therapy, alone or preceding chemotherapy, offers a potential strategy for managing chemoresistant tumors.
- Further research is warranted to explore the mechanisms and clinical utility of interferon in overcoming drug resistance.