Morphos Declared a "Breakthrough Therapy" for Lymphoma
MorphoSys’s main objective is to design exceptional and unique biopharmaceuticals, all designed to enhance the lives of patients suffering from severe or life-threatening conditions.
The human body has two types of lymphocytes that can develop into lymphomas: B lymphocytes (B cells) and T lymphocytes (T cells). B cells make up over 85% of non-Hodgkin lymphoma (NHL) cases. Diffuse large B-cell lymphoma (DLBCL) is the most common form of NHL and is responsible for more than 30% of all newly diagnosed cases of NHLs in the United States. Around 30-40% of patients with DLBCL either experience relapse or do not respond to initial treatment.
“DLBCL is a very aggressive lymphoma. In particular, those patients who fail standard treatments are in need of more therapeutic options. We look forward to working closely with the FDA and to develop MOR208 as a potential new treatment option for these patients as quickly as possible” said Dr. Malte Peters, Chief Development Officer of MorphoSys AG.
Innovative technologies and development approaches are continuously being put to use in order to further develop and review new drug prospective, either alone or in combination with other drugs. If a new drug can demonstrate substantial evidence of its functional improvement over existing treatment options, it may be granted approval.
This new breakthrough therapy
The FDA has granted a “breakthrough therapy” for lymphoma, more specifically: MOR208 in combination with Lenalidomide, for the treatment of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma, who are not qualified to receive high-dose chemotherapy and autologous stem-cell transplantation. MOR208 is an Fc-enhanced monoclonal antibody that targets CD19, which is thought to be an important element in B-cell receptor signaling. It is underway in clinical development for its presence in blood cancer.
The new breakthrough therapy is based on data gathered from the ongoing phase 2 L-Mind study. The findings presented at the American Society of Clinical Oncology 2017 meeting, showed a complete response of 32% and an objective response of 56%. “We are very excited having seen the preliminary data from the first 44 patients of our ongoing phase 2 L-MIND trial. We are particularly optimistic about the level of response rates that we have seen so far, especially complete responses. For DLBCL patients who relapse after their first-line treatment, current treatment options are very limited. We are therefore exploring potential new treatment regimens with MOR208 for this difficult-to-treat patient group” said Dr. Peters. L-Mind study’s overall objective is to measure progression-free survival, overall survival, duration of response, overall response rate, as well as safety.
How this therapy impacts overall survival
“For MorphoSys, relapsed/refractory DLBCL is a key development focus. We expect to report further data from our ongoing phase 2 L-MIND trial with MOR208 plus lenalidomide at this year's American Society of Hematology conference in December. In addition, we are currently evaluating MOR208 in combination with bendamustine in our phase 3 B-MIND trial. MorphoSys intends to speed up and potentially broaden the development of MOR208 in other indications of unmet need” commented Dr. Peters. Besides the phase 2 L-Mind study, the phase 2/3 B-Mind study began in August of 2016 and moved into phase 3 in June of 2017, based on sufficient data from its initial safety assessment.
The B-MIND study is intended to assess the safety and effectiveness of MOR208 in combination with bendamustine, for the treatment of patients with R/R DLBCL, who are not qualified to receive high-dose chemotherapy and autologous stem cell transplantation. It also aims to compare and contrast rituximab in combination with bendamustine.
Furthermore, it intends to evaluate several factors, including progression-free survival, overall survival, duration of response, objective response rate, time to progression, disease control rate, and patients’ quality of life. Currently, MOR208 in combination with idelalisib or venetoclax is being examined as a possible alternative for patients with R/R CLL after the discontinuation of Bruton tyrosine kinase inhibitor therapy.
The reason for the development of either Hodgkin’s lymphoma or non-Hodgkin’s lymphoma is not completely understood. However, what is known is that the origin of the lymphoma is vital to determining a proper prognosis and treatment regime. Diffuse large B-cell lymphoma is treated with rituximab and cyclophosphamide, vincristine (Oncovin), hydroxydaunorubicin, prednisone, and bleomycin (R-CHOP), though new possible alternatives are ongoing in clinical development.
Studying CAR T-cell therapy
As of last year, another study looked into therapy with the chimeric antigen receptor (CAR) T-cell as a possible option for treatment of refractory non-Hodgkin’s lymphoma. “KTE-C19 is an anti-CD19 CAR T cell therapy. It’s a cellular therapy. Patients who would be eligible for it undergo a procedure called apheresis, that is sort of like hemodialysis, where we take out their cells and ship them to Kite Pharma and their manufacturing facility. The cells are manufactured in a closed and streamlined process that takes about 6 to 8 days. We then are able to give a little bit of chemotherapy to remove the normal lymphocytes, and infuse the CAR T-cells. The CAR T-cells are re-programmed in the manufacturing facility. A gene is inserted into the cells to re-target them against the lymphomas, specifically a target called CD19. When we infuse those back into the patient, we can see relatively fast remissions in patients who really have no other treatment option” said Frederick L. Locke, physician and bone marrow transplant specialist.
Dr. Locke and his research team conducted a ZUMA-1 study in order to assess the safety and effectiveness of KTE-C-19 in patients with refractory aggressive B-cell non-Hodgkin’s lymphoma. All patients were 18 years old or older and had previously undergone anti-CD20 therapy and a treatment plan containing anthracycline. In phase 1 of the study, researchers noticed complete remission in the patients and overall safety. In phase 2, they analyzed two cohorts: patients with diffuse large B-cell lymphoma (cohort 1) and patients with primary mediastinal B-cell lymphoma / transformed follicular lymphoma (cohort 2). After receiving a three day, low-dose chemotherapy regime comprised of cyclophosphamide and fludarabine, patients received a dose of KTE-C19. 6 patients with cohort 2, who received KTE-C19 and underwent follow-up after 30 days, were found to have an objective response of 100% and underwent complete remission.
In cohort 1, 17% of patients experienced grade 3 or grade 4 cytokine-release syndrome and 29% experienced grade 3 or grade 4 neurologic toxicity. However, as far as these side effects go, Dr. Locke commented that the toxicities were reversible and controllable. “KTE-C19 can lead to high overall response rates and high complete remission rates in patients who really have no treatment options. The manufacturing success rate was also quite remarkable; 99% of patients enrolled in the study were able to have their CAR T-cells manufactured; and the toxicities were manageable across 22 different centers” said Dr. Locke. Still, “the ZUMA-1 trial is a pivotal trial that is expected to support FDA approval for this therapy” concluded Dr. Locke.
Researchers are looking closer into what causes lymphoma, how to improve treatment, and how to advance long-term benefits. Recent studies on monoclonal antibodies, man-made replicas of immune system proteins, show promising results in targeting lymphoma cells and triggering fewer side effects. Thus far, immense effort by hospitals, medical centers, and other facilities all around the world is ongoing into researching lymphoma, in hopes of discovering new treatment options for patients with certain types of lymphoma.