Every Cure Collaborates on New Publication in the American Journal of Hematology Highlighting Promising Repurposing Opportunity for Rosai-Dorfman-Destombes Disease (RDD)

Rosai-Dorfman-Destombes disease (RDD) is a rare condition where overactivated immune cells (histiocytes) build up throughout the body, leading to abnormal masses in the skin, lymph nodes, bones, and internal organs. Patients with this condition are often left with limited treatment options for this disease which can become life-threatening when it affects vital organs. A new publication in the American Journal of Hematology may offer hope. Led by collaborators at the Dalhousie University, Every Cure, and other leading institutions, the study demonstrates that a combination of two existing drugs, lenalidomide and dexamethasone (often called “len/dex”), can be an effective and well-tolerated treatment for patients with difficult-to-treat RDD. At Every Cure, we are proud to have contributed to this work by using our computational pharmacophenomics platform and medical expertise to help validate this promising treatment approach.

A Promising Option for Patients with Limited Alternatives

RDD is a rare and complex disease, and treatment decisions are often challenging. While some patients may benefit from targeted therapies, these treatments depend on specific genetic mutations. Yet, about 60% of RDD patients do not have these targetable mutations.

Lenalidomide is an immunomodulatory drug that helps regulate the immune system and reduce inflammation, both key drivers of RDD. Dexamethasone, a corticosteroid, is often used alongside it to enhance its effects.

While the len/dex combination is already widely used in other blood-related conditions, it has not traditionally been a primary treatment for RDD. This study suggests it may deserve a more prominent role, especially because this combination:

Is widely available and generic
May be effective regardless of genetic mutation status
Is associated with manageable side effects

In this study, researchers retrospectively evaluated 11 patients with RDD, many of whom had already tried multiple treatments without success. While 11 patients may seem small, it represents a meaningful cohort for such a rare disease. All 11 patients received len/dex, with a median treatment duration of about 18 months. The results were compelling:

The treatment was generally well tolerated, with mostly mild side effects
10 out of 11 patients experienced clinical or radiographic improvement
Patient benefit observed even after multiple prior therapies had failed

For patients, this combination therapy may offer a meaningful and, in many cases, durable response. These findings address a key therapeutic gap in RDD, particularly for patients without targetable mutations or those who have exhausted conventional options. Patients without these mutations are typically treated with standard chemotherapies, which can have limited effectiveness and significant side effects.

Every Cure’s Contribution: Computational Pharmacophenomics

Alongside the retrospective study, Every Cure applied computational pharmacophenomics to systematically evaluate potential treatments for RDD. This emerging approach to systematic drug repurposing evaluates the therapeutic potential of all approved drugs across all diseases and disease subtypes (published in Lancet Haematology, 2025). At Every Cure, we typically use this approach to uncover the most promising repurposing opportunities irrespective of drug or disease; in this study, we applied it to identify and prioritize treatments for RDD.

This analysis examined nearly 3,000 FDA-approved drugs to predict which ones might be most effective for RDD. The results strongly supported the clinical findings:

Dexamethasone ranked 4th overall among all drugs evaluated and was the highest-ranked corticosteroid
Lenalidomide ranked 23rd overall, and even higher (3rd) when excluding standard chemotherapies and corticosteroids
Lenalidomide outperformed several commonly used treatments, including two nonsteroids recommended as first-line options

This alignment between computational predictions and real-world patient outcomes highlights the power of pharmacophenomics to uncover high-impact treatment opportunities.

From Data to Real-World Impact

One of the most compelling aspects of this study is how computational predictions and clinical care came together. For example, patients who had not responded to multiple prior treatments including chemotherapy, immunotherapy, and targeted therapies, experienced significant improvement on len/dex. This is exactly the kind of impact Every Cure aims to enable: identifying effective treatments faster and getting them to patients who need them most.

A Collaborative Effort

This work was led by an outstanding group of collaborators, including Dr. Luke Chen and the team at the Coastal Rare Inflammatory Diseases (CoRID) program, with lead authorship by Dr. Emily Leung, resident physician at the University of British Columbia. The effort also included contributions from experts across the U.S. and Canada, as well as the Every Cure team, including Dr. Nick Fragola, Dr. Elliot Sharp, Piotr Kaniewski, and Dr. David Fajgenbaum. We are deeply grateful to all of our collaborators for their leadership, clinical expertise, and shared commitment to improving care for patients with rare diseases.

Looking Ahead

This study highlights an important truth: many life-changing treatments may already exist, and we just need better ways to find them and get them to patients.

By combining clinical insight with computational pharmacophenomics, we can systematically uncover these opportunities and bring them to patients faster, especially in rare diseases where traditional drug development is often not feasible.

Read the full paper here.