CHIP and Multiple Myeloma: Impact on Stem Cell Transplant & Survival Rates

What is Clonal Hematopoeisis?

‘As people age, it is normal for their blood-forming cells, known as hematopoietic stem cells (HSCs), to acquire genetic mutations, or misspellings, in their DNA. Most of these mutations do not affect how HSCs function or cause disease. In some cases, however, the mutations give certain HSCs an edge in survival, granting them an outsized role in producing blood cells. When this situation arises in people who are otherwise healthy, it’s known as clonal hematopoiesis of indeterminate potential (CHIP). 

Individuals with CHIP do not have symptoms of disease or markedly abnormal blood counts, but their risk of developing a blood cancer such as leukemia is 10 times higher than average. That translates into a 1% chance per year of developing one of these diseases. People with CHIP also have an increased risk of cardiovascular disease and of leukemia resulting from treatment for other cancers.’

CHIP and Stem Cell Transplant

A recent article from the journal Nature Communications (authored by a team from Dana Farber Cancer Institute) reminds us of the relationship between multiple myeloma and CHIP, which stands for Clonal Hematopoeisis of Indeterminate Potential. CHIP may significantly impact multiple myeloma patients who are or will be undergoing Stem Cell Transplants (SCT). The Dana Farber team studied the prevalence of 224 mutated genes that tend to be present in the blood of those with hematological malignancies. 

Findings:

• CHIP was present in close to 22% of the myeloma patients studied.
• DNMT3A was the most frequently mutated gene, followed by: TET2, TP53, ASXL1, and PPM1D. 
• The median age at ASCT in patients with CHIP was 61 years, compared to 57 years in those without CHIP. 
• The presence of CHIP was associated with a history of smoking, a past medical history of cancer, and a decreased efficiency of stem cell mobilization.
• Patients with CHIP did not respond as well to induction therapy. 
• The median overall survival (OS) of patients with CHIP was 5.3 years, significantly lower than in those without CHIP (7.5 years).
• CHIP was also associated with a lower median progression-free survival (PFS) of 2.2 years compared to 2.6 years in those without CHIP. 
• Patients with CHIP prior to transplant do not have a higher risk of another hematological cancer compared to patients who do not have CHIP.
• When a patient begins a maintenance regimen with an immunomodulator (medicines that change your immune system to work more effectively), you will have a higher risk of developing a hematological cancer, regardless of whether you have CHIP or not.
• The presence of CHIP did not increase the risk among those receiving first-line IMiD maintenance or IMiD maintenance at any point after transplant. 

Conclusions From This Study:

• Maintenance with immunomodulators is associated with improved outcomes for all patients (CHIP or not).
• For patients who did not receive IMiD maintenance, CHIP was associated with a significantly lower median OS of 3.6 years (compared to 6.6 years in those who did not have CHIP mutations).
• These results suggest the presence of an interaction between the effect of having CHIP and maintenance therapy with immunomodulators (IMiD). (If you have had a stem cell transplant, it is wise to stay on your IMiD’s maintenance unless your physician tells you otherwise.)

‘Altogether, these data suggest that the presence of CHIP at time of transplant does not increase the risk of secondary cancers associated with IMiD maintenance and that patients with CHIP, when treated with IMiD maintenance, obtain a survival benefit similar to that seen in multiple myeloma patients generally.’ 

If you have not yet been tested for CHIP (your chances increase with age), you may want to speak with your physician. If you have CHIP and you are not yet refractory to IMiDs, you may want to continue with lenalidomide (Revlimid) maintenance (or one of the other immunomodulators).

Further research on CHIP and multiple myeloma is ongoing. Catch up on the latest advancements presented at medical conferences with HealthTree University for Multiple Myeloma.

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Source: 

• Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant