Astonishing Clinical Trial Results Show Promise for Non-Hodgkin Lymphoma Research
There’s good news for those who’ve been diagnosed with the aggressive non-Hodgkin lymphoma (NHL) type referred to as diffuse large-B cell (DLBCL). According to the American Cancer Society (ACS), this type of HNL is the most common type of lymphoma.
The descriptive letters clarify the type of white blood cell where the cancer originated. (In this case, it began within the diffuse large-B cells.) According to the ACS, large B- cells make antibodies which protect us from bacterial and viral invasions. Those antibodies attach to the trespassers as a signal to other parts of the immune system to destroy these invaders. The DLBCL type of NHL is the most common type for Americans.
Clinical trial results
Regarding the treatment of DLBCL, there’s breaking news on fantastic results of a recent study. A loud “bravo” goes out to Massachusetts General Hospital (MGH), Boston, for their recent research results posted online via Medical Press on August 28, 2017. In their clinical study, a 68-year-old woman demonstrated an amazing remission achieved by a targeted drug study.
The report came from a letter sent by MGH to the New England Journal of Medicine (NEJM) and which was posted in the journal. The patient’s NHL had spread to the brain, and was a condition referred to as a Central Nervous System tumor (CNS tumor).
According to MGH, one month after the woman received chemotherapy followed by IV infusion of the study drug JCAR017, her brain tumor was in full remission.
What’s even more amazing is the patient’s DLBCL cells had been resistant to chemotherapy, and a stem cell transplant had also failed. Her condition was deemed as terminal, with less than six months to live. Luckily, targeted therapy attacks the DLBCL cells in a manner different than chemotherapy does. That patient’s offending cells were remarkably receptive to this new line of attack and she went into spontaneous remission (MGH).
A second remission
In fact, and this is the most amazing part, when she developed a second tumor about two months later, after the surgical biopsy was performed, the study drug reactivated and she went into full remission again.
Such targeted treatments are relatively new and have become the up and coming frontier in clinical drug studies. These pharmaceuticals are considered to be part of a growing field of cancer treatment modalities broadly known as immune-system-based cancer therapy. The ACS informs us that other targeted therapy drugs are already being used to target other types of NHL.
The particular type of intervention in the research study is referred to as CAR-T-cell therapy. CAR-T therapy uses this different class of chemicals to target the immune system and mobilize its role in activating the immune system to do its primary job: fight off infection and illness (ACS).
A fascinating thing about this therapy (scientifically known as Chimeric antigen receptor [CAR] T-cell therapy), is how the treatment is prepared.
How is this treatment prepared?
According to the ACS, the process involves an alteration of T-cells, which is a type of white blood cell often referred to as “killer cells.” T-cells are a mainstay of the immune system. First, the T-cells are removed from the patient’s blood sample. In the lab, they are genetically engineered to create specific types of receptors on the cell surfaces. “These receptors are created to attach to certain proteins on the surface of the lymphoma cancer cells”.
Dictionary.com, under cell biology, explains this important-to-grasp concept of cell surface receptors: “any of various specific protein molecules in surface membranes of cells and organelles to which complementary molecules, as hormones, neurotransmitters, antigens, or antibodies, may become bound”.
In this particular study, per MGH, an anti-tumor chemical called JCARO17 was used to bind to CD19 protein, present on most DLBCL leukemias and lymphomas. (This clinical trial was sponsored by Juno Therapeutics.)
Once engineered, the T-cells are multiplied and returned to the patient’s blood. Because of the receptor factor, the T-cells are attracted to the lymphoma cells and attach to them. The “captured” cancer cells are then killed by the exterminator T-cells (ACS).
In the study being cited, the totally unexpected result in the older woman was “the first report of a response to CAR T-cells in a central nervous system lymphoma.” Most amazingly, the woman’s second tumor that presented about 2 months after her initial treatment, also went into remission. Blood studies showed an increase of her CD19-targeted cells in relation to the tumor’s remission. Although she relapsed and died the following year, the tumor never returned (Medical Press).
MGH noted that an increase of CAR T-cells has been observed with other immunotherapy drugs, but this was the first report of such a response to a biopsy.
Treatment options after relapse
MGH notes the implications of the study, not only for secondary DLBCL (as in the woman’s 2nd tumor) but also for primary CNS Lymphoma. Unfortunately, with the primary onset, treatment choices have been scant after a relapse. Few patients with primary CNS Lymphoma have survived.
According to the ACS, the cancerous condition CNS Lymphoma attacks the brain or spinal cord. It’s aggressive and eventually spreads throughout the CNS, to include tissues surrounding the cord, or even an eye.
The ACS also informs us that although CNS Lymphoma tends to be relatively rare, those afflicted are generally older or who have immune system issues secondary to transplants or HIV/AIDS, for example.
They list the symptoms of CNS Lymphoma to include headaches, confusion, and vision problems. Weakness in the face, arms, or legs may also occur, along with possible seizures.
The ACS also notes that the prognosis for primary CNS Lymphoma is poor, yet consider the concurrent factors of older age or other serious health conditions as a factor.
"Brain involvement in DLBCL carries a grave prognosis, and the ability to induce a complete and durable response with conventional therapies is rare," explains Jeremy Abramson, MD, of the MGH Cancer Center, lead author of the letter in the Aug. 24 NEJM. "In addition, all available CAR T-cell trials have excluded patients with central nervous system involvement.”
How this new treatment is not typical
"Typically, the drugs we use to fight cancer and other diseases wear off over time," Abramson explains. "This spontaneous re-expansion after biopsy highlights this therapy as something entirely different, a 'living drug' that can re-expand and proliferate in response to biologic stimuli."
He and his co-authors note that discovering the mechanisms behind the reactivation of CAR T-cells could further augment their efficacy.
Meanwhile, research on lymphoma continues. For instance, the University of Southampton is conducting a Phase I drug study for treatment of certain types of DLBCL. The standard treatment for DLBCL is referred to as R-Chop. This approach includes rituximab, an immunotherapy drug, in combination with four chemotherapy drugs. In an attempt to improve patient treatment-response, they are working with Astro-Zeneka to study the effects of the replacement of rituximab with a new drug called acalabrutinib (Medical Press).
Dr. Andrew Davies, lead researcher on the trial and associate professor and consultant in medical oncology at the University of Southampton, said: "For some lymphoma patients, standard treatments are not effective, so we urgently need trials like this to help more people survive their disease.”
References
https://medicalxpress.com/news/2017-08-team-response-central-nervous-tumor.html
https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/types-of-non-hodgkin-lymphoma.html
https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/new-research.html
https://medicalxpress.com/news/2017-08-experimental-drug-trial-treatment-lymphoma.html
