Introducing Novel Treatment Option for Rare Disease AL Amyloidosis

A new clinical trial for AL amyloidosis is paving the way for a promising new treatment option for patients with the rare organ-debilitating disease. Results from the phase 2 study, published online Feb. 21 in the Journal of Clinical Oncology, determined that the chemotherapy-steroid drug combination—bendamustine with dexamethasone—is a viable, effective treatment for patients with relapsed AL amyloidosis. 

The multi-center phase 2 clinical trial was led by Suzanne Lentzsch, MD, PhD, professor of medicine at Vagelos College of Physicians and Surgeons at Columbia University. Dr. Lentzsch directs Columbia’s Multiple Myeloma and Amyloidosis program, is an oncologist at New York-Presbyterian, and a member of the Herbert Irving Comprehensive Cancer Center (HICCC). Dr. Lentzsch also initiated the Columbia Multidisciplinary Amyloidosis Program (CAMP) that provides a multidisciplinary treatment approach for patients with AL Amyloidosis. 

“AL amyloidosis  is very often a late-recognized disease with high mortality rates. Patients can suffer from systemic organ failure,” says Dr. Lentzsch. “As of today, we don’t have an FDA approved drug to treat AL amyloidosis. Our findings give hope and a viable alternative to patients who really have limited effective and safe treatment options at this point in their care.” 

Addressing an unmet need for amyloidosis

In the United States, each year around 4,500 new cases are diagnosed with AL amyloidosis, a rare disease that stems from the unruly production of amyloid. AL (or free light-chain) amyloidosis is the most common and deadliest form of the disease. AL amyloidosis occurs when bone marrow cells, or plasma cells, produce abnormal antibodies called light-chains. Infiltrating virtually all organs including vital organs like the heart and kidney, AL amyloidosis can lead to severe organ damage or in some cases, organ failure. 

To date, there are no established treatments for AL amyloidosis, specifically for patients who have relapsed and  are no longer responding to a drug regimen. AL amyloidosis is particularly hard to treat because it is challenging to diagnose; typically, patients remain undiagnosed for years while being treated only for organ-related problems. 

The disease can be associated with multiple myeloma (MM), a blood and bone marrow cancer that also stems from uncontrollable plasma cells. The two are closely related in their histology and sometimes overlap; in which case patients are diagnosed with both AL and MM. While treatments for MM have been established and have proven effective for newly diagnosed AL amyloidosis patients, AL patients typically do not tolerate certain drug regimens for MM such as the Revlimid. “This is the patient population our multi-center trial wanted to target. These are the patients that don’t have any viable treatment options to turn to,” notes Dr. Lentzsch. 

What the findings reveal 

In previous studies, the chemotherapy drug bendamustine administered on its own proved to be well tolerated, especially by multiple myeloma patients. Given the efficacy and tolerability of bendamustine in the treatment of MM, the investigators set out to evaluate its use in combination with the steroid, dexamethasone for AL amyloidosis patients in relapse and who are not tolerating other therapies. 

The trial enrolled 31 patients who received a combination dosage of bendamustine and dexamethasone (ben-dex) in 28-day cycles. Patients were treated up until their disease progressed or up to six cycles after attaining a full, positive response from the regimen. The study demonstrated that 57% of patients experienced a partial or better response to the treatment, with 11% achieving a complete positive response to the medication. The new combination therapy was tolerated well by the participants, even very sick patients, without such side effects as organ dysfunction that prior studies have not been able to achieve. Only a small percentage of patients in the trial experienced minor side effects, such as fatigue and nausea. 

The study, which spanned six different institutions, is the first prospective phase II trial of combination ben-dex for the treatment of relapsed or refractory AL amyloidosis. In addition to the HICCC at NewYork-Presbyterian/Columbia, the trial was co-led by investigators at Tufts Medical Center, Karmanos Cancer Institute at Wayne State University, Tisch Cancer Institute at Mount Sinai School of Medicine, the Amyloidosis Center at Boston University, and Memorial Sloan Kettering Cancer Center. 

“Since there has been no approved treatment for this patient population,” says Dr. Lentzsch, “these results provide a real option for patients and will make a difference in treating AL amyloidosis, safely and effectively.”