Medicine seldom progresses in dramatic steps. Its jagged progress is more commonly achieved by a prudent synthesis of its existing arsenal and the unheralded broadening of access to its gifts. The past few years have have provided examples. Innovative techniques have begun opening the doors to kidney transplantation to patient groups previously denied access, just as thoughtfully formulated cocktails of chemotherapeutic agents have improved outcomes for some metastatic colorectal cancer patients and some treatment refractory leukemias. High risk sensitized candidates have been consistently hard to transplant for many years. These candidates generate a host of antibodies against almost every donor antigenis in all likelihood neutering everything before them.
Now, thanks to the work done by the team from the University of Pennsylvania, we have a form of a CAR T-cell therapy similar to those used for blood cancers that can obliterate some of these antibodies, and help sensitized candidates become candidates once again. In the initial trial of this technique, two possible recipients who could not receive a double kidney transplant due to their overwhelming preexisting sensitivity went from near total recipients to decrease antibodiesnearing institution minus a life-saving kidney for each of them. This therapy Definitely does not remove the necessity of being paired with an appropriate donor, butitnearnest3/4sthereshoes.
Meanwhile, others are working to free transplant recipients from the disease of daily immune suppression. UCLA has developed a delayed tolerance protocol, where donor stem cells are infused months, even years after the original transplant. Whereas some of the original patients on this new protocol have been able to discontinue their anti-rejection medications completely, improving both their health and quality of life, it is still limited to carefully selected cases.
Cancer is also following a similar logic of combination in this setting. Patients with metastatic colorectal cancer whose tumors harbor this particular genetic signature, dMMR or MSI-H, often respond to immunotherapy now a large trial has demonstrated that use of chemotherapy and bevacizumab in combination with atezolizumab reduces the risk of disease progression or death by over half compared to immunotherapy alone. Progression-free survival median extended from roughly 5 months to over 2 years. Response rates increased Much as well. Definitely this is not applicable to all colorectal cancer patients, but for this molecularly defined subgroup it offers a clearer more effective initial approach. Leukemia research is converging as well.
Relapsed acute myeloid leukemia has proven difficult to treat due to formidable stem cells that persist through current therapies. Preclinical and early translational studies have found a three-drug combination involving the novel agent inobrodib as well as two approved drugs. In advanced models of disease the triplet did almost eradicate the leukemia stem cells responsible for relapse. Patient derived samples evidenced significant killing of tumor cells even relative to the most active single agent or doublet. Clinical studies are the logical next step, but the preclinical results may be sufficient to start that discussion.