Super ASK Patient: Re-Engineered Blood Cells Successfully Treat Mary Beth’s Relapsed Lymphoma


In early 2016, Mary Beth Smith was getting ready to retire after almost 40 years as a morning radio broadcaster in Toldeo, Ohio. She was an active 62-year-old working mom. She loved walking her two dogs everyday, learning to play pickleball, reading voraciously, spending quality time with her husband—the love of her life for 27 years, and watching their daughter and two sons grow into thriving adults. 

However, her life was quickly interrupted by a relapse of non-Hodgkin’s lymphoma (NHL), which she had first dealt with in 2012. Here, she shares her story.

How were you first diagnosed with non-Hodgkin’s lymphoma?

In November of 2012, I thought I was having an appendicitis issue. A CT scan revealed several swollen lymph nodes in my abdominal cavity—totally unrelated to the appendicitis discomfort; I truly believe the saying, “coincidence is God’s way of remaining anonymous.”

A second CT scan and a surgical biopsy proved the lymph nodes were diffuse large B-cell lymphoma (DLBCL), and I immediately began six treatments of R-CHOP chemo, three weeks apart. Subsequent PET scans showed I was crystal clear of the cancer—and I remained so for two years.

What happened after those two years?

A routine PET scan in 2015 revealed the cancer had returned, but this time in the form of follicular cancer—a much lower grade—and requiring no treatment; just a “watch-and-wait” process which could take many years to manifest itself into anything serious.

In early 2016, the follicular lymphoma had transformed into the diffuse large B-cell, and I was then on track for a more rigorous course of treatment: a stem cell transplant of my own cells. This is not an easy process; it requires harsh chemotherapy and then the transfer of your cells back into your body. Unfortunately, two follow-up PET scans showed the transplant did not work for me.

At that point, you reached out to Cancer Commons. How did you hear about ASK Cancer Commons?

Again, coincidence (God’s way) intervened, and I heard from a friend of many years, Jude LaCava, who had started the Dorothy Foundation in honor of his mother who had died from cancer. He was wondering how I was doing, and when I told him about my latest challenges, he recommended I get in touch with Cancer Commons. Specifically, he said to contact chief scientist Emma Shtivelman who researches all the possible clinical trials available to patients like me.

How has Dr. Shtivelman helped you?

Dr. Shtivelman was a godsend who took me from desperation to hope in a matter of a few emails. She sent me many clinical trial possibilities and particularly focused on a relatively new and still experimental immunotherapy known as CAR T-cell infusions. These infusions use your own white blood cells (T-cells), which are sent to a lab for several weeks to be re-engineered to fight the cancer in your system. In other words, your own blood cells attack the cancer.

I also contacted the Leukemia and Lymphoma Society (LLS) because they also have a nurse navigator who studies clinical trials. She also said CAR T-cell therapy was the latest treatment that seemed to be having encouraging results. When I cross-referenced the material from Cancer Commons and LLS, I came up with several matching clinical trials involving the CAR T-cell treatment. The goal was to find one near my home in Toledo, if I could. And to find one that would accept me sooner than later.

You ended up enrolling in a CAR T-cell trial at Cleveland Clinic last November. How did you decide on that specific trial?

My local oncologist knew the hematologist/oncologist at Cleveland Clinic who was well versed in CAR T-cell treatment. This physician was able to see me reasonably quickly and the next thing I knew, I was #3 on the list to become part of their clinical trail. Within weeks, I had moved up to #1 on the list and the process really accelerated from there.

From November through December 2016, I went through extensive testing required by the Kite pharmaceutical company to determine if I met their criteria for entry into the clinical trial. This included a biopsy of my cancer nodes, a bone marrow biopsy, a lumbar puncture, a heart and lung evaluation, and numerous blood tests to make sure I had no infections, viruses, or any inflammation. When all was said and done, I appeared to be an excellent candidate for this trial. I was reasonably healthy and the cancer was considered a low-burden disease that had not spread beyond my abdominal area.

What was it like to receive CAR T-cell treatment in the trial?

On December 5, 2016, my blood cells were taken from my body via apheresis and immediately shipped to the Kite pharmaceutical lab in California to be re-engineered. On December 27, 2016, after 3 days of pre-conditioning chemo done outpatient, I was admitted to the Cleveland Clinic and at noon my “re-engineered” blood cells were blessed by the hospital chaplain and were infused back into in my body. The process took less than 15 minutes. When it was over, I felt nothing. And I panicked a bit thinking those beefed-up blood cells should be wreaking havoc on my system. For 6 days, absolutely nothing happened. I was convinced it hadn’t worked. And then January 1, 2017, the cytokine storm or cytokine response syndrome kicked in! Happy New Year to me—Happy Hellish New Year to my husband.

For 36 hours I was comatose. My body and mind were in a catatonic state. I felt nothing and remember nothing about it. But my husband has never been so terrified and subsequently suggested to Cleveland Clinic personnel that maybe he could have been better prepared for what the results can be from the “storm.” Unfortunately, because this is a clinical trial, the results can be different for every patient. They try to tell you everything they’ve seen—which is why the consent form is 33 pages long and daunting. But until your loved one is actually going through the storm, you can’t really imagine the response.

Once I came out of the “storm,” my only real symptoms were extreme fatigue and weakness. And after less than two weeks in the hospital, I was able to go home to recover. All I wanted to do was sleep. I wasn’t even interested in eating. Thankfully, my husband was able to use his powers of persuasion to get me to go to physical therapy, and he also kept me well-stocked in bottles of Ensure.

January 23, 2017, we returned to the Cleveland Clinic for a PET scan to see how the T-cells had done. Our doctor walked in and immediately gave us the news: a complete response to the treatment—no sign of cancer. I even made him show me the PET scans side by side just to make sure nothing had been missed. The new PET scan had nothing on it. It was a true miracle that had my husband and I crying and then hugging the doctor and our clinical trial nurse. It was unbelievable! We feel so blessed. And prayers do work!

What comes next?

I will be going back to the Cleveland Clinic for frequent check-ups and blood work. And PET scans will be a part of my regular routine over the next several months/years. And I must admit, the PET scans and waiting for the results still leave me feeling anxious and nervous. This is part of my new normal now. In between, I would just like to get stronger and healthier and enjoy the retirement that started a year ago but got detoured.

What advice would you give to someone who is newly diagnosed?

My best advice: you must be your own health advocate. Ask lots of questions and don’t give up when you don’t get satisfactory answers. Whatever type of cancer you have, contact Cancer Commons and the national organization of your type of cancer, and ask about any clinical trials that might be suitable for you. At the very best, you could be put on a path to your own miracle. Secondly, you could be a pioneer that will help someone else find their own miracle.

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Super Patients are cancer survivors who learned to be more engaged in their own care. Cancer Commons believes every patient can be a Super Patient or benefit from a Super Caregiver. We hope these stories will provide inspiration and hope for your or your loved one’s own treatment journey.


Cancer Patients Benefit from Isavuconazole, a New Antifungal

The gist: This article describes the results of a clinical trial—a research study with volunteer patients. The goal of the study was to test a new treatment for fungal infections in cancer patients. The researchers found that the new drug, isavuconazole, is just as effective as the existing drug voriconazole, and it has fewer bad side effects,

“A newly developed antifungal, isavuconazole, is as effective as an existing drug, voriconazole, against invasive mold disease in cancer patients with less adverse effects, according to phase 3 clinical data presented at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy, an infectious disease meeting of the American Society for Microbiology.

” ‘There is a growing need for new antifungal therapies like isavuconazole because serious fungal infections caused by Aspergillus and other molds are on the rise due to the increasing numbers of immunosuppressed patients, including those with active cancer. These infections are associated with high morbidity and mortality. If approved, isavuconazole has the potential to be an important new option for the treatment of these life-threatening fungal infections,’ says Andrew Ullman of Julius Maximilians University in Wuerzburg, Germany, one of the researchers presenting data.

“Invasive fungal infections are important causes of morbidity and death for patients with hematological malignancies. Many leukemia and lymphoma patients receive high-dose chemotherapy, sometimes followed by stem cell transplantation, compromising their immune systems. The genus Aspergillus comprises several hundred species of mold that are ubiquitous in the environment but pose little threat to people with healthy immune systems. Immunocompromised patients, however, are more vulnerable to infection.”


R2CHOP Appears Highly Active in DLBCL

Editor’s note: This article describes the results of a clinical trial—a research study with volunteer patients. The trial tested a new treatment for newly diagnosed diffuse large B-cell lymphoma (DLBCL). The new treatment consists of a combination of chemotherapy drugs known as R-CHOP, plus a new drug called lenalidomide (aka Revlimid). R-CHOP is a standard treatment for DLBCL. The results were promising, but more research will need to be done to figure out whether the new treatment is indeed better than the old. The results also showed that adding lenalidomide might work better for a certain sub-group of patients known as the non-GCB subtype.

“The combination of lenalidomide and R-CHOP demonstrated considerable activity in patients with newly diagnosed diffuse large B-cell lymphoma, according to results of a phase 2 study.

“The development of a more effective initial therapy is essential to improve long-term outcomes of patients with diffuse large B-cell lymphoma (DLBCL), Grzegorz S. Nowakowski, MD, of the division of hematology at Mayo Clinic in Rochester, Minn., and colleagues wrote.

“Prior studies demonstrated lenalidomide (Revlimid, Celgene) has considerable single-agent activity in relapsed DLBCL. Lenalidomide also can be combined with R-CHOP — which consists of rituximab (Rituxan; Genentech, Biogen Idec), cyclophosphamide, doxorubicin, vincristine and prednisone) — to form a novel combination known as R2CHOP.

“In the current study, Nowakowski and colleagues evaluated the efficacy of R2CHOP in 60 patients with newly diagnosed DLBCL. The median age of patients was 65 years; 70% were aged older than 60 years, and 9% were aged ≥80 years.”


Vitamin D Deficiency Worsens Outcomes With B-Cell Lymphoma

“Vitamin D deficiency (VDD) contributes to worse outcomes in elderly patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, according to a study published online Aug. 18 in the Journal of Clinical Oncology.

“Jörg Thomas Bittenbring, MD, from Universitätsklinikum des Saarlandes in Germany, and colleagues examined the impact and mechanisms of VDD in patients with DLBCL. Chemoluminescent immunoassays were used to evaluate 359 pretreatment 25-hydroxyvitamin D3 serum levels from the RICOVER-60 study (6 Versus 8 Cycles of Biweekly CHOP-14 With or Without Rituximab) and 63 from the RICOVER-noRTh study (an amendment to the RICOVER-60 study).

“The researchers found that RICOVER-60 patients treated with rituximab with VDD (≤8 ng/mL) had 3-year event-free survival (EFS) of 59% and 3-year overall survival (OS) of 70%, while those with vitamin D levels >8 ng/mL treated with rituximab had EFS and OS of 79 and 82%, respectively. In multivariate analysis adjusting for International Prognostic Index risk factors, these differences remained significant, with hazard ratios of 2.1 (P = 0.008) for EFS and 1.9 (P = 0.040) for OS. In all 7 individuals with VDD, there were significant increases in rituximab-mediated cellular cytotoxicity (RMCC; P < 0.001) after substitution and normalization of their vitamin D levels.”


Innate Pharma: Orphan Drug Designation in the European Union for IPH4102

Editor’s note: When a newly developed drug for a rare (“orphan”) disease seems particularly promising for patients, the European Commission may choose to grant it “orphan drug designation.” The designation removes certain barriers that might otherwise keep a drug company from being able to successfully develop and profit from the drug in Europe. A new drug called IPH4102 has just received an orphan drug designation for the treatment of cutaneous T-cell lymphoma (CTCL).

“Innate Pharma SA (the “Company” – Euronext Paris: FR0010331421 – IPH), the innate immunity company developing first-in-class drug candidates for cancer and inflammatory diseases, today announced that the European Commission has granted orphan drug designation to IPH4102 for the treatment of cutaneous T-cell lymphoma (CTCL).

“CTCL is a group of rare cutaneous lymphomas of T lymphocytes with poor prognosis and few therapeutic options at advanced stages. IPH4102 is a first-in-class cytotoxic anti-KIR3DL2 antibody, aiming at destroying CTCL cancer cells.
Hervé Brailly, Chief Executive Officer and co-founder of Innate Pharma, said: ‘This decision by the European Commission validates the IPH4102 approach in a disease with significant medical need and supports our strategy for a rapid clinical development’.

“Phase I trial with IPH4102 is expected to begin in 2015.”


Bortezomib/Lenalidomide Combination Therapy Evaluated in Relapsed/Refractory Mantle Cell Lymphoma

Editor’s note: This article describes the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to test the effectiveness of a mantle cell lymphoma treatment that combines the drugs bortezomib (Velcade) and lenalidomide (Revlimid). Specifically, the trial tested the treatment for patients whose cancer did not get better after previous treatments or whose cancer returned after treatment. The results of the clinical trial were “disappointing.” The combination treatment was less effective than either drug on its own.

“Although the majority of patients with mantle cell lymphoma respond to initial therapy, the duration of remission is typically short (1.5 to 3 years). Although bortezomib (Velcade) and lenalidomide (Revlimid) as single agents have been associated with response rates as high as 53% in patients with relapsed/refractory disease, Morrison et al reported an overall response rate of almost 40% with combination bortezomib/lenalidomide therapy in an article published in Leukemia & Lymphoma.

“The incidence of mantle cell lymphoma has increased dramatically over the past several decades. The median overall survival is 3 to 6 years with standard chemotherapy approaches, and fewer than 15% of patients are long-term survivors.

“Therefore, researchers continue to investigate newer therapeutic options for these patients. One such approach was the combination of bortezomib and lenalidomide, particularly in patients who experienced relapse from or were refractory to previous treatments. In the phase II CALGB 50501 trial, a team of investigators from the University of Minnesota, Duke University, Dana-Farber Cancer Institute, Ohio State University, Washington University, and Georgetown University attempted to evaluate the feasibility of combination treatment with bortezomib and lenalidomide in patients with relapsed or refractory mantle cell lymphoma.”


Lymphoma Treatment May Harm, Halt Men's Sperm Production

“Treatment for lymphoma may lower men’s fertility, new research indicates.

“Both Hodgkin lymphoma and non-Hodgkin lymphoma, which are cancers of the body’s white blood cells, often affect young people who are still in their reproductive years. For men, treatment for these cancers can harm or halt sperm production. Although most men regain their fertility within two years of treatment, the researchers cautioned that men should be counseled about the possibility of this significant side effect before treatment begins.

” ‘While many men can look forward to their fertility returning after treatment is over, not all will be so fortunate,’ Dr. Rebecca Sokol, president of the American Society for Reproductive Medicine, said in a society news release. ‘It is imperative that prior to the initiation of therapy, counseling and sperm preservation be made available to all lymphoma patients and their partners who may want to have children in the future.'”


FDA Approves Zydelig for Three Types of Blood Cancers

“The U.S. Food and Drug Administration today approved Zydelig (idelalisib) to treat patients with three types of blood cancers.

“Zydelig is being granted traditional approval to treat patients whose chronic lymphocytic leukemia (CLL) has returned (relapsed). Used in combination with Rituxan (rituximab), Zydelig is to be used in patients for whom Rituxan alone would be considered appropriate therapy due to other existing medical conditions (co-morbidities). Zydelig is the fifth new drug with breakthrough therapy designation to be approved by the FDA and the third drug with this designation approved to treat CLL.

“The FDA is also granting Zydelig accelerated approval to treat patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL), another type of non-Hodgkin lymphoma. Zydelig is intended to be used in patients who have received at least two prior systemic therapies.

“ ‘In less than a year, we have seen considerable progress in the availability of treatments for chronic lymphocytic leukemia,’ said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. ‘Zydelig’s approval to treat CLL reflects the promise of the breakthrough therapy designation program and represents the FDA’s commitment to working cooperatively with companies to expedite a drug’s development, review and approval.’ ”


Mayo Clinic Recommends New Routine Testing for some Non-Hodgkin Lymphomas

Editor’s note: Testing a patient’s tumors for mutated genes can give doctors important information about that patient’s outlook and appropriate treatments. This article discusses two predictive mutations that doctors can test for in the tumors of people with anaplastic large-cell lymphoma (ALCL) who have already been found not to have a mutation in the ALK gene.

Excerpt:

“A Mayo Clinic-led group of researchers has discovered three subgroups of a single type of non-Hodgkin lymphoma that have markedly different survival rates. These subgroups could not be differentiated by routine pathology but only with the aid of novel genetic tests, which the research team recommends giving to all patients with ALK-negative anaplastic large-cell lymphoma (ALCL). Findings are published in the journal Blood.

“Patients whose lymphomas had TP63 rearrangements had only a 17 percent chance of living five years beyond diagnosis, compared to 90 percent of patients whose tumors had DUSP22 rearrangements. A third group of tumors, those with neither rearrangement, was associated with an intermediate survival rate.

“ ‘This is the first study to demonstrate unequivocal genetic and clinical heterogeneity among systemic ALK-negative anaplastic large-cell lymphomas,’ says Andrew L. Feldman, M.D., a Mayo Clinic pathologist and senior author on the multi-institutional study. ‘Most strikingly, patients with DUSP22-rearranged ALCL had excellent overall survival rates, while patients with TP63-rearranged ALCL had dismal outcomes and nearly always failed standard therapy.’ Dr. Feldman also is a Damon Runyon Clinical Investigator.”