Researchers explore optimal induction therapies for managing blood cancer

Dec 7 2009

There have been significant scientific advances in the field of blood cancers, and leading experts continue to gain a better understanding of how certain diseases progress in order to discover new treatment options and provide patients with the best care. Research presented today at the 51st Annual Meeting of the American Society of Hematology explores optimal induction therapies for managing multiple myeloma, the importance of advance care planning for improved quality of life, and a potential new first-line therapy for patients with non-Hodgkin lymphoma.

"Studies such as these are designed to improve the quality of evaluation, diagnosis, and treatment of various blood cancers," said moderator of the press conference Richard A. Van Etten, M.D., Ph.D., Director of Tufts Medical Center Cancer Center in Boston. "The results of these studies not only give hematologists a better understanding of disease progression, but also direct them to the measures that are safer and more effective in treating their patients."

This press conference will take place on Saturday, December 5, at 10:00 a.m.

A Prospective, Multicenter, Randomized Trial of Bortezomib/Melphalan/Prednisone (VMP) Versus Bortezomib/Thalidomide/Prednisone (VTP) as Induction Therapy Followed by Maintenance Treatment With Bortezomib/Thalidomide (VT) Versus Bortezomib/Prednisone (VP) in Elderly Untreated Patients With Multiple Myeloma Older Than 65 Years [Abstract #3]

Multiple myeloma is a type of blood cancer that affects white blood cells known as plasma cells and is common among the elderly. In the United States, the incidence of this disease is increasing at an alarming rate with 13,000-15,000 new cases diagnosed each year. Over the last few years the treatment of elderly patients older than 65 years with multiple myeloma has changed, mainly due to the introduction of novel agents such as thalidomide, bortezomib, and lenalidomide. According to results from the Velcade as Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone (VISTA) trial, the combination of bortezomib, melphalan, and prednisone is significantly superior to melphalan and prednisone alone, which has been the current standard of care for multiple myeloma patients who cannot receive a stem cell transplant. However, research has not yet confirmed whether an alkylating agent (chemical compound) or an immunomodulatory therapy (drug that suppresses or stimulates the body's immune response) is the optimal partner for bortezomib. Researchers from the Spanish Myeloma Group designed a study to better determine if melphalan or thalidomide should be used as part of induction therapy (the initial treatment given to patients) in combination with bortezomib. The study showed that elderly patients were able to receive less aggressive treatment regimens of induction therapy by supplementing them with a maintenance treatment.

In order to evaluate whether the induction therapy regimen could be further optimized by decreasing toxicity while maintaining efficacy, the intensity of both treatment regimens was reduced as compared with the VISTA regimen, but supplemented with maintenance therapy. In this study, 260 patients with a median age of 75 years were randomized to receive a modified induction schedule of six cycles of bortezomib, melphalan, and prednisone (VMP) or bortezomib, thalidomide, and prednisone (VTP) as induction therapy followed by maintenance therapy with bortezomib and thalidomide (VT) or bortezomib and prednisone (VP) for up to three years.

Study results indicate that modified induction schedules for both VMP and VTP were highly effective with similar overall response rates (80 percent for VMP and 81 percent for VTP), which were determined using the European Group for Blood and Marrow Transplantation (EBMT) criteria, and complete remission rates (20 percent for VMP and 27 percent for VTP), but there was a clear difference in the toxicity profile of each group. In the VMP regimen there was a higher incidence of neutropenia (abnormally low count of white blood cells) and infections, but VTP resulted in the development of cardiac toxicity. The frequency of grade 3-4 peripheral neuropathy (PN) was 5 percent in the VMP group. Maintenance therapy with either VT or VP also markedly improved the quality of patient responses with a good safety profile, increasing complete response from 23 percent up to 42 percent, with no significant differences in response rates between the VT and VP treatment arms. In addition, both maintenance regimens resulted in an acceptable toxicity profile.

"Melphalan with prednisone has been the gold standard for the treatment of elderly multiple myeloma patients for the past 40 years, but novel combination therapies have emerged as superior options," said lead author Maria-Victoria Mateos, M.D., Ph.D., Attending Physician, Hematology Department at the Hospital Universitario de Salamanca in Spain. "In this study, we demonstrate that the combination of a reduced dosage for induction therapy followed by maintenance therapy may be a novel approach for treating this patient population."

Dr. Mateos will present this study at the Plenary Scientific Session on Sunday, December 6, at 2:30 p.m. in Hall F.

Psychological Correlates of Having Advance Care Planning in Patients With Hematological Malignancies [Abstract #72]

Advance care planning (ACP) provides patients with the opportunity to communicate with their family and health-care provider about their end-of-life choices. Patients who participate in ACP usually have a living will and a health-care proxy, a person who carries out their health-care choices in the event that they become incapable of making medical decisions. However, according to previous studies, only 50 percent of patients with blood cancers who are undergoing a high-risk procedure, such as a stem cell transplant, participate in ACP. Moreover, the group that lacked ACP had a higher mortality rate, suggesting that the group least likely to have ACP is the group most in need of it. While there is a need to increase engagement in ACP, many argue that discussing possible death with patients adds to their stress level. Researchers from the University of Nebraska Medical Center in Omaha and Fred Hutchinson Cancer Research Center in Seattle compared the psychological well-being of patients with blood cancers who did or did not have ACP to help understand how best to design interventions that may increase patient engagement in ACP.

This study analyzed data from the HEMA-COMM (Hematology Communications) study cohort, an observational study that evaluated doctor-patient communication. The study included 293 patients with blood cancers who have ACP - that is, have a designated health-care proxy and a living will - or who did not have ACP - that is, they lacked a health-care proxy or a living will, or both. The two groups were compared according to socio-demographic characteristics, diagnosis, previous treatments, patient and physician estimates of cure and life expectancy, discussions of wishes for life support, and various measures of psychosocial well-being including coping, depression/anxiety, denial, social support, and quality of life.

The study found that both patients who engage and who do not engage in ACP have similar psychosocial well-being except for patterns of coping. Patients who have ACP use more problem-focused coping patterns (e.g., taking advice, active coping, seeking moral support or discussing feelings with others, planning, and having a positive outlook) as opposed to emotion-focused coping patterns (e.g., denial, behavioral or mental disengagement, turning to religion, self-blame, and substance abuse). Problem-focused coping is defined as problem solving by doing something to alter the source of stress and predominates when a person feels that something constructive can be done to affect the outcome of events. In addition, patients with ACP were more likely to be older (56 years versus 52 years), have higher income, have leukemia or myelodysplastic syndrome, and have received prior cancer treatment. The majority of patients with ACP discussed wishes for the use of life support with family (62 percent), while only 30 percent had discussed their wishes with a physician with or without family, and just 8 percent of patients had not discussed their wishes at all.

"While advance care planning may be more relevant for someone who has a life-threatening disease, it really is important to all individuals, and we hope that more people engage in this important process," said lead author Fausto R. Loberiza Jr., M.D., Associate Professor at the University of Nebraska Medical Center. "In order to increase engagement in ACP, it is important to focus on the practical importance of ACP regardless of prognosis and de-emphasize the emotional aspects of ACP. This approach may be more appealing to our patients regardless of coping style."

Dr. Loberiza will present this study in an oral presentation on Sunday, December 6, at 5:45 p.m. in Room 393-396.

Bendamustine Plus Rituximab is Superior in Respect of Progression-Free Survival and Complete Remission Rate When Compared to CHOP Plus Rituximab as First-Line Treatment of Patients With Advanced Follicular, Indolent, and Mantle Cell Lymphomas - Final Results of a Randomized Phase III Study on StiL (Study Group indolent Lymphomas, Germany) [Abstract #405]

About half of all blood cancers are those of the lymphatic system, which are classified as either Hodgkin or non-Hodgkin lymphoma. There are many types of non-Hodgkin lymphoma, including follicular lymphoma (the second most common type) and mantle cell lymphoma (a rare and difficult-to-treat cancer). While the current standard of care for patients with non-Hodgkin lymphoma is a chemotherapy regimen called CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone) plus the immunotherapy rituximab, it has been linked to high toxicity rates. However, promising results have been observed in two phase II studies evaluating a new combination treatment consisting of a chemotherapy agent called bendamustine plus rituximab in patients with relapsed or refractory indolent (slow-growing) or mantle cell lymphoma. In order to further investigate the role of bendamustine and rituximab combination therapy, researchers from the German Study Group Indolent Lymphoma (StiL) initiated a multicenter, randomized, phase III study to compare the efficacy and safety of bendamustine plus rituximab versus CHOP plus rituximab as a potential first-line therapy for patients with follicular, indolent, and mantle cell lymphoma.

Five hundred forty-nine patients were randomized to receive one dose of rituximab (375 mg/m2) plus two doses of bendamustine (90 mg/m2) every 28 days or the standard CHOP regimen every 21 days for a maximum of six cycles. The types of non-Hodgkin lymphoma were equally distributed between the two treatment regimens (55 percent and 56 percent for follicular lymphoma, 18 percent and 19 percent for mantle cell lymphoma, and 27 percent and 24 percent for other indolent lymphomas, respectively). The primary objective of the study was to improve progression-free survival for patients with non-Hodgkin lymphoma.

Study results revealed that bendamustine and rituximab combination therapy significantly improved progression-free survival and complete remission rates while showing less toxicity as compared with the current standard treatment. The median progression-free survival for bendamustine and rituximab combination therapy was 54.8 months compared with 34.8 months for CHOP and rituximab combination therapy. The complete remission rate of 40.1 percent for bendamustine and rituximab combination therapy was significantly higher than the 30.8 percent achieved with CHOP and rituximab combination therapy. As predicted, a higher frequency of serious adverse events was seen with the CHOP and rituximab combination therapy, such as neutropenia (10.7 percent versus 46.5 percent) and leukocytopenia (12.1 percent versus 38.2 percent). The bendamustine and rituximab combination therapy was better tolerated by patients as evidenced by lower rates of treatment side effects such as hair loss (15 percent versus 62 percent), infectious complications (95 versus 121 patients), nerve damage (18 versus 73 patients), and episodes of inflammation in the mucous lining of the mouth (16 versus 47 patients).

"While the CHOP and rituximab combination is the current standard of care, it is frequently associated with serious adverse events and more side effects, as was further shown in this study," said lead author Mathias J. Rummel, M.D., Ph.D., Head of the Department for Hematology at the University Hospital in Giessen, Germany. "These promising results suggest that the combination of bendamustine and rituximab has the potential to become the new standard, first-line treatment option for patients with these non-Hodgkin lymphoma entities."

Dr. Rummel will present this study on Monday, December 7, at 11:00 a.m. in Room 208-210.

SOURCE American Society of Hematology