HIV and Blood Cancers: The City of Hope Patient

The September 15 Institute for Value-Based Medicine® session hosted by The American Journal of Managed Care® and City of Hope, the National Cancer Institute–designated center based in Duarte, California, featured a presentation by Jana Dickter, MD, associate clinical professor in the Division of Infectious Disease, and Ahmed Aribi, MD, hematologist and assistant professor, Division of Leukemia, Department of Hematology and Hematopoietic Cell Transplantation.

First, Dickter outlined how the success of antiretroviral therapy is allowing people with HIV to live well past age 50 years—but this population has a higher risk of cancer. She cited data collected from 1996 to 2012 showing that persons with HIV had a 69% increased risk of all cancers (including those related to AIDS), and a 21% higher risk of non–AIDS-defining cancers.¹

The cumulative effects of HIV therapies, including toxicity, come at a price—including potential bone disease, renal disorders, cardiovascular disease, and liver effects. And that’s before considering the escalating cost of HIV therapy, which reached $22 billion in 2018. “Many first-line drugs [cost more than] $4000 a month,” Dickter said.

Yet it’s essential for persons with HIV to be treated, because keeping the viral load undetectable prevents transmission. “Because of the toxicities, we need to consider alternatives to chronic medication therapy to treat HIV, and there are exciting approaches for looking for a cure,” she said. This is where City of Hope has particular expertise, which led to a news-making discovery earlier this year.² Physicians reported a “cure” of a patient who had developed AIDS when he was aged in his 30s back in 1988, at the height of the AIDS crisis, and had survived thanks to HIV medications, but he also had a history of hepatitis B, which 2 of the HIV medications controlled.

As the patient reached his early 60s, he developed myelodysplastic syndrome, which ultimately converted to acute myeloid leukemia (AML). After chemotherapy, his HIV regimen was changed to allow for an allogeneic stem cell transplant. As Dickter explained, the best available donor carried a specific mutation, homozygous CCR5Δ32, “which is a rare genetic mutation that confers resistance to most strains of HIV.”

Post transplant, the patient stayed on his HIV therapy; he was vaccinated against hepatitis B and was later found to have adequate antibody projection. After 2 years, reservoir testing showing no significant levels of HIV, and the patient consented to stop HIV medications. “His viral load has remained undetectable to date,” Dickter said. “He’s now 3.5 years post transplant, has been off antiretroviral drugs for more than 18 months, and has no evidence of replicating HIV. His leukemia is also in remission.”

A handful of other patients have achieved HIV remission after stem cell transplant, but at age 63 years, the City of Hope patient is the oldest and had lived with HIV the longest. Information from this patient suggests “that some HIV patients with hematologic malignancies may not need fully intensive immunosuppressive therapies prior to their stem cell transplant in order to put them in remission from HIV,” Dickter said, and it may open new possibilities for treating older patients—if the right donors can be found.

Aribi spoke next, highlighting the increased likelihood of blood cancers as people age; AML is the most common type. The percentage of people who survive AML also decreases with age, with those older than 75 years having a 5-year survival rate of 2%.

Aribi then walked through the history of treatment regimens AML beginning in 1973, when anthracyclines became standard; to hypomethylating agents, which are more tolerable to older patients; to the most recent, targeted therapies, including IDH1 and IDH2 inhibitors. Ongoing clinical trials are examining combinations of these agents, and venetoclax as well. Other studies involve targeting T cells with PD-1 inhibitors nivolumab and pembrolizumab, and still others involve chimeric antigen receptor T-cell therapies targeting CD33, CD123, and CD70. Venetoclax is approved with hypomethylating agents for use in older, unfit patients.³

Aribi concurred with Dickter’s assessment of the cancer risk seen in older patients with HIV, and he reviewed cases involving prior allogenic transplants. A 2019 trial of 17 patients found potential for this option; graft-vs-host disease (GvHD) of grade 2, 3, or 4 was seen in 41% of the patients.⁴

“Management of antiretroviral medication during transplant is complicated because there is a lot of drug-drug interaction” activity between the antiretroviral agent and the immunosuppressive conditioning antibiotic, he said.

Thus, Aribi said, the City of Hope patient was very fortunate. There were actually 2 transplant donors available with the specific HIV-resistant mutation, which was usual. The patient developed refractory AML while awaiting transplant. It took 3 regimens to achieve remission from AML to do the transplant, Aribi said. Ultimately, the patient had only mild GvHD post transplant: “Even heavily pretreated, with 3 regimens prior to his transplant, the patient did very well.” 

References
1. Hernández-Ramírez RU, Shiels MS, Dubrow R, Engels EA. Cancer risk in HIV-infected people in the USA from 1996 to 2012: a population-based, registry-linkage study. Lancet HIV. 2017;4(11):e495-e504. doi:10.1016/S2352-3018(17)30125-X
2. Johnson M. Longtime HIV patient is effectively cured after stem cell transplant. The Washington Post. July 27, 2022. Accessed September 27, 2022. https://www.washingtonpost.com/science/2022/07/27/hiv-remission-stem-cell-transplant-city-of-hope/
3. NCI staff. FDA approvals bring new options for older patients with AML. National Cancer Institute. December 27, 2018. Accessed September 27, 2022. https://www.cancer.gov/news-events/cancer-currents-blog/2018/fda-approval-glasdegib-venetoclax-aml-older
4. Ambinder RF, Wu J, Logan B, et al. Allogenic hematopoietic cell transplant for HIV patients with hematologic malignancies: the BMT CTN-0903/AMC-080 trial. Biol Blood Marrow Transplant. 2019;25(11):2160-2166. doi:10.1016/j.bbmt.2019.06.033