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Haematological Disease
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Many patients are asymptomatic when diagnosed on routine blood counts and require no active therapy apart from monitoring. If the CLL progresses (e.g. with cytopenias, lymphadenopathy or B symptoms), treatment is indicated. Treatment depends on the patient's functional status and can vary from chemoimmunotherapy (with fludarabine- and rituximab-containing regimes) to low-dose single-agent chemotherapy. The Bruton's TKI ibrutinib and the pro-apoptotic agent venetoclax are promising and are increasingly used in difficult-to-treat cases.
Non-Hodgkin Lymphoma
Published in Tariq I. Mughal, Precision Haematological Cancer Medicine, 2018
It is of note that the WHO has now recognized that all grade 3B patients, but perhaps not 3A, should be treated as DLBCL. Clearly the distinction between these histological grades, based on the sheets of centroblasts, can be difficult and needs refinement. Many treatment guidelines, including the NCCN and British Society of Haematology (BSH), for the therapy of patients with FL with extensive, but not bulky stage 2 or more disease include watch-and-wait approach as ‘reasonable’ in patients who have grade 1, 2 or 3A histology, are totally asymptomatic, have no organ dysfunction attributable to FL and there is no firm evidence of steady progression. Clearly, in some clinical scenarios, the patient’s preference, the physician’s enthusiasm and the definitive proof (or lack of) needs to be aligned. FL patients who relapse following chemoimmunotherapy with chemosensitive disease are subjected to high-dose chemotherapy followed by an auto-SCT. Unfortunately, long-term remissions following auto-SCT are rare.
Malignant Neoplasms of the Rectum
Published in Philip H. Gordon, Santhat Nivatvongs, Lee E. Smith, Scott Thorn Barrows, Carla Gunn, Gregory Blew, David Ehlert, Craig Kiefer, Kim Martens, Neoplasms of the Colon, Rectum, and Anus, 2007
Another approach is combination immunotherapy and chemotherapy Chemoimmunotherapy aims at combining the “debulking” capacity of chemotherapy with the potential of immunotherapy for controlling microscopic disease and therefore producing long-term disease-free survival.
Progress in the application of hydrogels in immunotherapy of gastrointestinal tumors
Published in Drug Delivery, 2023
Hao Zheng, Meng Li, Lili Wu, Wenshang Liu, Yu Liu, Jie Gao, Zhengmao Lu
Currently, for late-stage cancers with distant metastases, chemoimmunotherapy with reduced systemic toxicity and strong efficacy is essential. Several "cocktail" formulations have been reported that combine chemotherapeutics inducing immunogenic cell death (ICD) with immune adjuvants and alginate to induce localized chemoimmunization therapy (Chao et al., 2020). The ICI antibody can either be included in this cocktail for local administration or injected intravenously. The gelation of ALG in place after injection into solid tumors would induce local retention and sustained release of therapeutics, thereby reducing the systemic toxicity of the treatment. With the help of immune adjuvants, chemotherapy-induced ICD triggers an immune response specific for tumors, which is magnified by ICIs to produce activated systemic immune responses against cancer in devastating regional tumors, eliminating metastases and restraining cancer reappearance. The tumor-localized cocktail chemoimmunotherapy strategy that integrates clinically common agents holds great promise for clinical translation.
Advances in therapeutic strategies for primary CNS B-cell lymphomas
Published in Expert Review of Hematology, 2022
Safaa Ramadan, Tommaso Radice, Ahmed Ismail, Stefano Fiori, Corrado Tarella
To date, Ibrutinib and lenalidomide seem to be the most effective novel therapies in CNS lymphomas, but these agents are not associated with durable responses as monotherapy. Unfortunately, when combined with chemoimmunotherapy, considerable toxicity and mortality have been reported. Therefore, dose adjustment and appropriate supportive and anti-infective therapies should be incorporated to render these new protocols more tolerable, in particularly in older and heavily pretreated patients with poor performance status and compromised organ reserve. PD-1 blockade showed also promising results in PCSNL. The inclusion of these new drugs in first-line chemoimmunotherapy protocols is necessary to improve the outcome of PCSNL patients and is thought to be more tolerable in this setting. Clinical trials are still ongoing to optimize combination protocols with the aim of reducing toxicity and maintaining responses. CAR-T-cell therapy has shown efficacy in patients with secondary SCNSL with few, but quite encouraging, results in PCNSL. These results need to be confirmed in ongoing prospective clinical trials that also test the intraventricular administration of CAR-T-cell treatment. The role of CAR-T cell therapy is of particular interest as a salvage second and third-line treatment.
Exploiting gene mutations and biomarkers to guide treatment recommendations in mantle cell lymphoma
Published in Expert Review of Hematology, 2021
In the present review we summarized the currents status of prognostic factors in MCL and their impact on managing patients. Though the list of prognostic factors reported has grown substantially, they so far had limited impact on how to decide on treatment options. The current standards of chemoimmunotherapy established over the last 3 decades have been essentially based on the dose intensity/age dichotomy. While there has been an improvement in the treatment of mantle cell lymphoma (MCL) in both median progression-free survival (PFS; >7–8 years) and overall survival (OS; >10–12 years), patients with high-risk features such as high risk MIPI (mantle cell international prognostic index), high Ki-67 (≥30%), or blastoid variants still carry poor outcome with a median OS of 3 years. Furthermore, patients with high-risk molecular features, such as TP53 mutations show dismal outcome, with a median OS of 1.8 years, regardless of therapy used. Other abnormalities are associated with worse outcome in particular complex karyotypes. In addition, RWD show a much more humbling reality with not only a great heterogeneity in the management of patients but a median PFS and OS well below ½ what has been observed in trials. On the other hand, RWD have also revealed the positive impact of novel therapies approved for the treatment of relapsed/refractory (R/R) MCL (6 new agents approved in the US), leading to durable responses and improved survival even in refractory or high-risk patients.