Tailored approaches to relapsed/recalcitrant myeloma found within NCCN guidelines

SAN FRANCISCO – The approach to relapsed/refractory multiple myeloma (MM) has to be tailored patient by patient based on the biology of the disease, frailty measures, comorbidities, and prior treatment regimens, Natalie Callander, MD, director of the myeloma clinical program at the University of Wisconsin Carbone Cancer Center, Madison, said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

Despite major treatment breakthroughs in recent years and a wide swath of therapeutic options, multiple myeloma is still an incurable disease that eventually relapses in most patients, Dr. Callander, vice chair of the NCCN Multiple Myeloma Panel, said. “If you are having trouble with your relapsed or refractory patients, you’re not alone.”

As a guide to individualize the treatment approach, the NCCN has put together recommendations for patients with relapsed/recalcitrant MM. “Preferred regimens” include bortezomib-lenalidomide-dexamethasone and other well-established combinations supported by evidence from Phase 1 trials. When relapse occurs more than 6 months after primary induction, one option is simply to repeat the induction therapy.

A long list of “other recommended regimens” includes 21 combination options supported by “very strong Phase 2 data,” she said. The NCCN also has a third list of regimens for the most aggressive disease and certain special circumstances. Two powerful combinations that are used to get the disease under control quickly include high-dose cyclophosphamide or dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide, (DT-PACE) with or without bortezomib.

Dr. Callander underscored the importance of differentiating biochemical relapse, such as increases in serum M protein or other indicators, from clinical relapse, such as new soft tissue plasmacytomas or hypercalcemia.

Patients with clinical relapse typically need a quicker and more vigorous therapeutic response, she said. Studies have found that those in biochemical relapse tend to do better than those in symptomatic relapse.

“This whole concept of biochemical versus symptomatic is really important,” Dr. Callander said.

Among the tips she offered for managing patients with relapse, were to perform a repeat bone marrow biopsy with cytogenetics to gauge the presence of high-risk biology, since this category of patients tends to do far worse and to need a more aggressive treatment approach.

“Getting that kind of information with that follow-up bone marrow biopsy might be very important,” she said.

It’s important to be aware of the phenomenon of “light chain escape,” in which patients with relapsed/refractory disease can stop making intact immunoglobulin G. It’s thought to be due to clonal evolution, in which the clone that was making intact immunoglobulin becomes less dominant. These patients tend to do worse than similar patients who don’t exhibit this phenomenon, Dr. Callander said.

Dr. Callander reported no relevant financial disclosures.

SAN FRANCISCO – The approach to relapsed/refractory multiple myeloma (MM) has to be tailored patient by patient based on the biology of the disease, frailty measures, comorbidities, and prior treatment regimens, Natalie Callander, MD, director of the myeloma clinical program at the University of Wisconsin Carbone Cancer Center, Madison, said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

Despite major treatment breakthroughs in recent years and a wide swath of therapeutic options, multiple myeloma is still an incurable disease that eventually relapses in most patients, Dr. Callander, vice chair of the NCCN Multiple Myeloma Panel, said. “If you are having trouble with your relapsed or refractory patients, you’re not alone.”

As a guide to individualize the treatment approach, the NCCN has put together recommendations for patients with relapsed/recalcitrant MM. “Preferred regimens” include bortezomib-lenalidomide-dexamethasone and other well-established combinations supported by evidence from Phase 1 trials. When relapse occurs more than 6 months after primary induction, one option is simply to repeat the induction therapy.

A long list of “other recommended regimens” includes 21 combination options supported by “very strong Phase 2 data,” she said. The NCCN also has a third list of regimens for the most aggressive disease and certain special circumstances. Two powerful combinations that are used to get the disease under control quickly include high-dose cyclophosphamide or dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide, (DT-PACE) with or without bortezomib.

Dr. Callander underscored the importance of differentiating biochemical relapse, such as increases in serum M protein or other indicators, from clinical relapse, such as new soft tissue plasmacytomas or hypercalcemia.

Patients with clinical relapse typically need a quicker and more vigorous therapeutic response, she said. Studies have found that those in biochemical relapse tend to do better than those in symptomatic relapse.

“This whole concept of biochemical versus symptomatic is really important,” Dr. Callander said.

Among the tips she offered for managing patients with relapse, were to perform a repeat bone marrow biopsy with cytogenetics to gauge the presence of high-risk biology, since this category of patients tends to do far worse and to need a more aggressive treatment approach.

“Getting that kind of information with that follow-up bone marrow biopsy might be very important,” she said.

It’s important to be aware of the phenomenon of “light chain escape,” in which patients with relapsed/refractory disease can stop making intact immunoglobulin G. It’s thought to be due to clonal evolution, in which the clone that was making intact immunoglobulin becomes less dominant. These patients tend to do worse than similar patients who don’t exhibit this phenomenon, Dr. Callander said.

Dr. Callander reported no relevant financial disclosures.

SAN FRANCISCO – The approach to relapsed/refractory multiple myeloma (MM) has to be tailored patient by patient based on the biology of the disease, frailty measures, comorbidities, and prior treatment regimens, Natalie Callander, MD, director of the myeloma clinical program at the University of Wisconsin Carbone Cancer Center, Madison, said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

Despite major treatment breakthroughs in recent years and a wide swath of therapeutic options, multiple myeloma is still an incurable disease that eventually relapses in most patients, Dr. Callander, vice chair of the NCCN Multiple Myeloma Panel, said. “If you are having trouble with your relapsed or refractory patients, you’re not alone.”

As a guide to individualize the treatment approach, the NCCN has put together recommendations for patients with relapsed/recalcitrant MM. “Preferred regimens” include bortezomib-lenalidomide-dexamethasone and other well-established combinations supported by evidence from Phase 1 trials. When relapse occurs more than 6 months after primary induction, one option is simply to repeat the induction therapy.

A long list of “other recommended regimens” includes 21 combination options supported by “very strong Phase 2 data,” she said. The NCCN also has a third list of regimens for the most aggressive disease and certain special circumstances. Two powerful combinations that are used to get the disease under control quickly include high-dose cyclophosphamide or dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide, (DT-PACE) with or without bortezomib.

Dr. Callander underscored the importance of differentiating biochemical relapse, such as increases in serum M protein or other indicators, from clinical relapse, such as new soft tissue plasmacytomas or hypercalcemia.

Patients with clinical relapse typically need a quicker and more vigorous therapeutic response, she said. Studies have found that those in biochemical relapse tend to do better than those in symptomatic relapse.

“This whole concept of biochemical versus symptomatic is really important,” Dr. Callander said.

Among the tips she offered for managing patients with relapse, were to perform a repeat bone marrow biopsy with cytogenetics to gauge the presence of high-risk biology, since this category of patients tends to do far worse and to need a more aggressive treatment approach.

“Getting that kind of information with that follow-up bone marrow biopsy might be very important,” she said.

It’s important to be aware of the phenomenon of “light chain escape,” in which patients with relapsed/refractory disease can stop making intact immunoglobulin G. It’s thought to be due to clonal evolution, in which the clone that was making intact immunoglobulin becomes less dominant. These patients tend to do worse than similar patients who don’t exhibit this phenomenon, Dr. Callander said.

Dr. Callander reported no relevant financial disclosures.