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Cancer
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Elyce Cardonick, Charlotte Maggen, Puja Patel
Burotto reported normal development of an infant at 11 months of age whose mother was treated with check point inhibitors ipilimumab (anti CTLA4) and nivolumab (anti PD-1) starting at 9 weeks x4 cycles for recurrent metastatic melanoma stage IV [101]. Masses decreased in size during pregnancy however autoimmune hepatitis developed. An iatrogenic PTB occurred at 32 weeks. Monoclonal antibodies are known to cross at higher rates late in the third trimester, how much a preterm delivery contributed to this reassuring outcome for the neonate is unknown. Mehta also reported normal development at 32 months after exposure to ipilimumab including during the first trimester [102].
Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Ipilimumab is administered intravenously usually through a course of four doses, one every three weeks. This agent has been associated with severe and potentially fatal immunological adverse effects due to T-cell activation and proliferation. Most of the other ADRs are GI-related and include stomach pain, bloating, constipation, and diarrhea. However, fever and breathing or urinating difficulties have also been reported. Due to this, a “risk evaluation and mitigation strategy” has been set up to inform prescribers of the potential risks.
Overview of Therapeutic Biomarkers in Cancer
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Sherry X. Yang, Janet E. Dancey Treatment
A significant breakthrough in the treatment of cancer across multiple cancer types is immunotherapy with monoclonal antibodies that target the immune checkpoints such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathway (Chapter 14). Currently, this class of antibodies that activate the immune system, but not limited to, include ipilimumab that blocks CTLA-4, tremelimumab, pembrolizumab and nivolumab that inhibit PD-1, as well as avelumab, atezolizumab, and durvalumab that target the PD ligand 1 (PD-L1). The three PDL1 antibodies are approved for the treatment of metastatic Merkel-cell carcinoma, advanced bladder cancer or NSCLC. Ipilimumab and pembrolizumab are indicated in the treatment of a range of cancer types including metastatic melanoma, NSCLC, small cell lung cancer, and HNSCC, hormone-refractory prostate cancer and advanced cervical cancer. Nivolumab is indicated for both BRAF wildtype and BRAF V600 mutation-positive unresectable or metastatic NSCLC progressed on or after platinum-based chemotherapy. It is also used for advanced renal cell carcinoma, classical Hodgkin’s lymphoma, and hepatocellular carcinoma in patients previously treated with sorafenib. In June 2020, it was approved for patients with recurrent or metastatic esophageal squamous cell carcinoma after prior platinum- and fluoropyrimidine-based chemotherapy.
Immune checkpoint inhibition in early-stage triple-negative breast cancer
Published in Expert Review of Anticancer Therapy, 2022
Revati Varma, Matthew Wright, Jame Abraham, Megan Kruse
Ipilimumab, an antibody against CTLA-4, is a commonly used treatment for numerous cancers. Comparatively, neoadjuvant ipilimumab in breast cancer has not been a robust area of investigation. In a pilot study by McArthur et al., women with early-stage breast cancer who were planning to undergo mastectomy received preoperative tumor cryoablation with or without ipilimumab, given as a single dose of 10 mg/kg IV. The combination regimen demonstrated safety and a beneficial immunologic response. This study included 18 patients with early stage HER2- breast cancer, including 3 patients with TNBC who were free of recurrence at a median follow-up of 66 months [45]. A similar study from this group in the same setting demonstrated that pre-operative cryoablation with both ipilimumab and nivolumab is safe and yielded a larger immune response with enhanced T cell activation compared to cryoablation with ipilimumab alone. These findings inform an ongoing single-arm phase II trial (NCT03546686) assessing 3-year EFS in women with operable TNBC who have residual tumor after receiving taxane based NACT. Patients will receive pre-operative ipilimumab, nivolumab and cryoablation as well as adjuvant nivolumab [46].
A functional antibody cross-reactive to both human and murine cytotoxic T-lymphocyte-associated protein 4 via binding to an N-glycosylation epitope
Published in mAbs, 2020
Dong Li, Jing Li, Huanyu Chu, Zhuozhi Wang
Due to the importance of CTLA-4 function, CTLA-4 blockade has been tested for treatment of cancer in numerous preclinical and clinical studies. A substantial amount of data has been published for two antibodies against CTLA-4, ipilimumab, and tremelimumab. Ipilimumab (MDX-010, BMS-734016) is an immunomodulatory agent that has been approved as monotherapy for treatment of advanced melanoma.9 Combined with an anti-PD-1 antibody, ipilimumab has also been approved for the treatment of advanced melanoma, metastatic colorectal cancer with MMR and MSI-H aberrations and renal cell carcinoma.10 Tremelimumab was evaluated as monotherapy in melanoma and malignant mesothelioma11 and in combination with the anti-PD-L1 antibody durvalumab in multiple cancers.12–15 Since human and mouse CTLA-4 only share approximately 76% amino acid identity, these two anti-CTLA-4 antibodies can only bind to human CTLA-4 (hCTLA-4), but not murine CTLA-4 (mCTLA-4).16 Here, we developed a novel antibody, mAb146, by immunizing rats with both human and mouse CTLA-4 and screening a large number of hybridoma clones. This antibody recognizes not only the MYPPPY motif that interacts with CD80/CD86, but also an N-glycosylated site epitope that is conserved in human, monkey, and murine CTLA-4.
Current treatment of lymphoma in pregnancy
Published in Expert Review of Hematology, 2019
Anna Gurevich - Shapiro, Irit Avivi
Nivolumab and pembrolizumab, anti PD1 antibodies used in refractory or relapsed HL, have not been examined with respect to pregnancy, but have been associated with an increased risk of fetal loss [89,90]. The PD-1/PD-L1 pathway plays an important role in maintaining maternal immune tolerance to the fetus during pregnancy [91]. Inhibition of this pathway could cause an immune-mediated response to the fetus with detrimental effects. Nivolumab administration resulted in a non–dose-related increase in spontaneous abortion and increased neonatal death in monkeys [92]. A single case report exists of treatment with nivolumab and ipilimumab during the first trimester with a normal progression of the pregnancy until week 32, when a healthy preterm newborn was delivered due to signs of placental insufficiency [91]. As mentioned earlier, brentuximab vedotin, approved for relapsed and refractory HL outside pregnancy, is contraindicated during the gestational period.