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    Topics Alert Archive

    Alert Number 301

    Campath in the News

    Date: October 27, 2024

    I doubt there are many CLL patients out there who have not heard of Campath (technical name is “alemtuzumab”). Rituxan and Campath are the two monoclonal antibodies that have revolutionized CLL therapy options.

    Campath has been in the news recently, with very interesting and encouraging results – for multiple sclerosis patients. I know, this is a bit of off-topic Alert, but I thought I would bring it to your attention anyway, for two reasons. First, my strictly layperson analysis of my database of CLL patients brings up an intriguing pattern – CLL is more common in people of Jewish origin, and the same is true of MS as well. I do not know whether more formal epidemiological studies exist showing the same genetic predisposition to these two diseases. If any of you folks out there know someone in your family or friends who have multiple sclerosis, I strongly suggest you bring this paper to their attention. There seems to be reason for optimism in using Campath for MS, especially in early stage MS. The Second reason is that the potential value of Campath in MS underlines the mechanism of action of this drug, something all CLL patients should understand.

    As we have pointed out several times on our website Campath targets the CD52 marker. This marker is carried by B-cells and T-cells, monocytes and neutrophils, all of them important cell lines of our immune system. As CLL patients with cancerous hordes of B-cells we are very happy that this monoclonal drug kills B-cells with great efficiency. However, it is not so wonderful for us that it kills T-cells as well. T-cells are our major line of defense against infections, especially viral infections. That is why Campath therapy guidelines now call for keeping a close watch on patients for potential viral reactivations, and many experts maintain their patients on preemptive anti-viral medications.

    In addition to the very real risk of increased infections due to across the board killing of B-cells and T-cells, there is one other fly in the ointment with Campath therapy for CLL patients. Once killed, the B-CLL cells do not stay killed for very long. Even for patients who received very deep “minimal residual disease negative” remissions, all too often the B-cells (CLL cells) grow back over a matter of several months. T-cells, on the other hand, take a very long time to recover. Even 1-2 years after Campath therapy T-cell populations are significantly depleted. In other words, CLL patients get the pointy end of the stick each time. The cancerous B-CLL cells come back sooner than we would like to see, and the infection fighting T-cells take their own sweet time.

    The scenario is exactly reversed for MS patients. In multiple sclerosis the damage to myelin sheath protecting nerve fibers is carried out by T-cells, a case of autoimmune disease where out of control rogue T-cells go on a rampage and attack the nerve sheaths. As expected, researchers saw that a one week administration of Campath killed off T-cells and B-cells in this MS study. Sure enough, the healthy B-cells grew back in a few months, providing the patients with a degree of immune protection. But the T-cell recovery took much longer, also as expected. This means that MS patients are likely to get long lasting protection against T-cell mediated autoimmune destruction of nerve fibers, and yet the quicker B-cell recovery gives them some degree of protection from infections. “What’s more, magnetic resonance imaging, or MRI, of the patients’ brains showed less inflammation in those getting alemtuzumab. The brain can wither in MS patients. Between months 12 and 36 in this study, interferon patients experienced a slight loss of brain volume on average whereas alemtuzumab patients added volume.” How cool is that!

    If you are a relative new comer to the CLL scene, here is the link to our website where you can find all the Campath articles. Knowledge is our best defense – what you and your oncologist do not know can surely kill you.

    Campath Therapy

    Be well,
    Chaya

    http://www.sciencenews.org/view/generic/id/37945/title/Drug_may_offer_MS_turnaround

    Drug may offer MS turnaround

    By Nathan Seppa

    Wednesday, October 22nd, 2024

    Leukemia drug improves multiple sclerosis symptoms in some people

    A disease thought to be incurable is now a step closer to losing that dispiriting reputation. Multiple sclerosis, the disabling neuromuscular disease that has resisted effective drug therapy, eases off in some people given a drug normally prescribed for leukemia, researchers report in the Oct. 23 New England Journal of Medicine.

    “More than half the patients in this study actually improved a significant amount” when taking the drug alemtuzumab, says study coauthor David Margolin, a neurologist at Genzyme Corp. in Cambridge, Mass., which teamed with an international team of researchers in conducting the trial. “We think this is something very special.”

    That optimism is tempered by worrisome side effects that showed up in MS patients taking the drug. Two more large-scale trials of MS patients are now getting under way to address those issues and confirm the positive findings.

    In MS, the body’s own immune cells orchestrate an attack on myelin, the fatty sheaths that insulate nerve fibers in the central nervous system. The origins of this mutiny remain a medical mystery, but the disaster that follows is well documented: A torrent of inflammation robs the nerves of their protective myelin, disrupting nerve signals and resulting in the motor control losses that mark MS. In the early stages, MS attacks often come and go in relapsing-and-remitting fashion. In the worst case scenario, the autoimmune assault becomes chronic, leading to irreparable nerve damage and permanent disability.

    Enter alemtuzumab, also called Campath. This drug targets a compound called CD52, which appears on T cells and B cells, the prime movers of the immune system. Alemtuzumab works well, killing off nearly all the T and B cells, and thus wiping out a huge portion of a person’s immune system. That’s a good thing if your immune cells are running amok, as in autoimmune disease or leukemia. But it can leave a person vulnerable to infection.

    Fortunately, this housecleaning is temporary. Since nascent T and B cells don’t make CD52, they escape the purge and go on to repopulate the immune system anew. That takes a few months for B cells but years for T cells, says study coauthor Alisdair Coles, a neurologist at the University of Cambridge in England.

    While the drug has helped patients fight chronic lymphocytic leukemia, testing against MS progressed slowly in the 1990s as researchers mainly tested alemtuzumab in advanced-stage, mostly middle-aged MS patients, with little success.

    That approach changed in 2024 when an international team of researchers began testing the drug on younger, less-advanced-stage MS patients over the course of a three-year trial. The scientists enrolled people mainly in their 20s and 30s with MS that was diagnosed only 1.3 years earlier, on average, and who hadn’t been treated for the condition yet.

    The researchers randomly assigned 111 to get interferon beta 1a, a standard MS drug given as three injections per week. Another 223 patients received alemtuzumab, delivered in a series of intravenous infusions over five days once a year. Most volunteers getting alemtuzumab got two series of infusions, one at the outset and another after 12 months; 46 received a third course a year after that.

    The interferon group was slated to receive regular injections during the three-year trial, but two-fifths stopped taking the drug at some point, most complaining of side effects or lack of effectiveness. All patients were monitored for three years.

    Clinical testing showed that disabilities for people on interferon rose on average during the trial but fell in those getting alemtuzumab, a first for a large trial, the authors point out.

    Overall, 57 percent of those on alemtuzumab improved during the study, while roughly one-fifth worsened and the others held steady. Of those getting interferon , one-third improved, 41 percent declined and the rest held even.

    Over the three years, only 20 percent of the alemtuzumab patients had a relapse, compared with 48 percent of the interferon patients.

    What’s more, magnetic resonance imaging, or MRI, of the patients’ brains showed less inflammation in those getting alemtuzumab. The brain can wither in MS patients. Between months 12 and 36 in this study, interferon patients experienced a slight loss of brain volume on average whereas alemtuzumab patients added volume.

    Combined, these findings suggest that the drug is somehow promoting brain repair in MS patients. “This is unprecedented. It hasn’t been seen before,” says Coles. “Up until now, no one would have thought this would happen.” He was particularly surprised by the MRI data. “Between 12 and 36 months,” he says, patients getting alemtuzumab “were actually acquiring new tissue in the brain.”

    The most common side effect from alemtuzumab concerns the thyroid gland, and 23 percent of patients getting the drug in this trial developed thyroid problems. In some people, the gland becomes overactive; in others, it became underactive. Of those getting inferferon, 3 percent developed thyroid problems.

    Immunologist Bibiana Bielekova of the National Institute of Neurological Disorders and Stroke in Bethesda, Md., says these thyroid problems are not always easy to treat. Plus, many patients with early-stage MS and mild symptoms might not relish the risk of developing a new problem, particularly when there are several other options available for treating their MS at that stage.

    On the other hand, Margolin says, thyroid problems, if manageable, “might be a fair trade off” since they aren’t as serious as MS.

    A dangerous bleeding disorder called ITP, or idiopathic thrombocytopenic purpura, showed up in 3 percent of alemtuzumab patients and 1 percent of interferon patients. ITP patients’ immune cells attack their own blood-clotting platelets, risking hemorrhage. One person on alemtuzumab died from the disorder.

    “We are quite aware of how incredibly effective this drug is,” Bielekova says. “But everybody is scared to death of those side effects.”

    Margolin says physicians will closely monitor patients’ platelet counts in the two upcoming trials of alemtuzumab.

    Previous studies had gauged alemtuzumab’s effects against MS largely in patients who had late-stage disease. The drug showed promise, but patients still went downhill, Bielekova says.

    Margolin suggests that using alemtuzumab to treat early-stage MS patients “who are still walking around” yields benefits because temporarily knocking out T cells and B cells quells the immune system’s ability to generate inflammation, an early-stage event in MS. “That seems to give the body a chance to recover,” he says.

    The new findings are “remarkable,” says Stephen Hauser, a neurologist at the University of California, San Francisco, writing in the same NEJM issue. This and previous work pitting alemtuzumab against MS represent “thoughtful clinical investigations [that] have advanced the field substantially,” he says. But only long-term testing will establish alemtuzumab’s place in the anti-MS armamentarium, he says.

    NOTICE: This page from the Topics Alert archive was originally emailed to subscribers of Topics Alert, a free service of CLL Topics Inc. If you are not a subscriber and you wish to receive email Alerts, please register at the Topics Alert subscription page. The content of this page is intended for information only and it is NOT meant to be medical advice. Please be sure to consult and follow the advice of your doctors on all medical matters.


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