Eligibility criteria for GT in SCD
| Inclusion criteria . | Exclusion criteria . | ||
|---|---|---|---|
| Criterion . | Justification . | Criterion . | Justification . |
| Age ≥18 years | Adult GT program | >1 α-chain deletion | Given the severe anemia and MDS-like disease seen in HGB-206 trial, this will be an exclusion criterion only for lovo-cel. |
| Optimized SCD pain regimen for ≥6 months | Necessary to determine potential benefit from relief of VOC | Recent neurosurgery or brain tumor precluding mobilization agents | Ineligible to be mobilized for stem cell collection |
| Diagnosis of severe SCD (with genotypes including βS/βS, βS/β0, βS/β+, βS/βC, βS/βD, βS/βO-Arab) with at least 1 of the following: | Goal to manage a severe sickle cell phenotype rather than specific genotypes given the mechanism of the approved GTs | Prior allogeneic HSCT or GT | Previously received curative or functional curative therapy |
| Recurrent vaso-occlusive crises (VOCs) (≥2 crises per year in prior 2 years, including priapism) | Consistent definition of severe SCD between the 2 trials | Presence of CCUS | Given that the presence of CCUS elevates the risk of secondary malignancy after transplant, we screen for this using molecular testing in patients referred for GT. |
| ACS (≥2 episodes in prior 2 y) | Consistent definition of severe SCD between the 2 trials | Active malignancy requiring treatment within 1 year | Ineligible for transplant as it would conflict with potential cancer therapy |
| History of CVA | Manifestation of severe SCD; criterion from lovo-cel trial | Advanced chronic liver disease (cirrhosis, bridging fibrosis, or active hepatitis) | Ineligible to receive myeloablative conditioning |
| Tricuspid regurgitant jet velocity >2.5 m/s | Manifestation of severe SCD; criterion from exa-cel trial | Cardiomyopathy (left ventricular ejection fraction <40%) | Ineligible to receive myeloablative conditioning |
| Severe lung disease (corrected DLCO <40%, SpO2 <85% [outside of VOC], clinically significant pulmonary hypertension [eg, requiring home oxygen]) | Ineligible to receive myeloablative conditioning | ||
| Kidney disease (eGFR <30 mL/min per 1.73 m2) | Ineligible to receive myeloablative conditioning | ||
| Clinically significant active infection (HIV-1/2, HBV, HCV, HTLV-1/2, tuberculosis, syphilis, toxoplasmosis, Trypanosoma cruzi, or West Nile virus) | Ineligible for transplant until active infection is well controlled | ||
| Cognitive or psychiatric impairment precluding safe therapy and recovery | Ineligible due to inability to comply with transplant precautions | ||
| CNS disease (untreated Moyamoya disease, uncontrolled seizure disorder, or debilitating physical impairment) | Ineligible per trials and/or ineligible to receive myeloablative conditioning | ||
| Other organ dysfunction precluding safe myeloablative conditioning (with busulfan) if not explicitly defined above | Ineligible to receive myeloablative conditioning | ||
| Pregnancy or breastfeeding | Ineligible to receive myeloablative conditioning | ||
| Inability to safety complete therapy (eg, lack of caregiver support, lack of stable housing, and nonadherence with medications, etc) | Patients must be able to attend visits to safely complete the entire process of GT. | ||
| Lack of insurance coverage for GT | A solvent GT program is needed to support patients during and after therapy. | ||
| Listed at other GT programs | Potential unfair advantage over other patients | ||
| Refusing a donor search | To have a complete discussion of alternative therapies, there must be a donor search. Patients may or may not be comfortable undergoing a related donor search for various reasons, but an unrelated donor search should be completed to ensure a full discussion of alternative therapies can be had and to maintain fairness for all patients, including those who may not be able to access allogeneic transplant due to lack of donor availability. This requirement ensures that all patients have the opportunity to explore all viable treatment options. This is also frequently an insurance requirement. | ||
| Inclusion criteria . | Exclusion criteria . | ||
|---|---|---|---|
| Criterion . | Justification . | Criterion . | Justification . |
| Age ≥18 years | Adult GT program | >1 α-chain deletion | Given the severe anemia and MDS-like disease seen in HGB-206 trial, this will be an exclusion criterion only for lovo-cel. |
| Optimized SCD pain regimen for ≥6 months | Necessary to determine potential benefit from relief of VOC | Recent neurosurgery or brain tumor precluding mobilization agents | Ineligible to be mobilized for stem cell collection |
| Diagnosis of severe SCD (with genotypes including βS/βS, βS/β0, βS/β+, βS/βC, βS/βD, βS/βO-Arab) with at least 1 of the following: | Goal to manage a severe sickle cell phenotype rather than specific genotypes given the mechanism of the approved GTs | Prior allogeneic HSCT or GT | Previously received curative or functional curative therapy |
| Recurrent vaso-occlusive crises (VOCs) (≥2 crises per year in prior 2 years, including priapism) | Consistent definition of severe SCD between the 2 trials | Presence of CCUS | Given that the presence of CCUS elevates the risk of secondary malignancy after transplant, we screen for this using molecular testing in patients referred for GT. |
| ACS (≥2 episodes in prior 2 y) | Consistent definition of severe SCD between the 2 trials | Active malignancy requiring treatment within 1 year | Ineligible for transplant as it would conflict with potential cancer therapy |
| History of CVA | Manifestation of severe SCD; criterion from lovo-cel trial | Advanced chronic liver disease (cirrhosis, bridging fibrosis, or active hepatitis) | Ineligible to receive myeloablative conditioning |
| Tricuspid regurgitant jet velocity >2.5 m/s | Manifestation of severe SCD; criterion from exa-cel trial | Cardiomyopathy (left ventricular ejection fraction <40%) | Ineligible to receive myeloablative conditioning |
| Severe lung disease (corrected DLCO <40%, SpO2 <85% [outside of VOC], clinically significant pulmonary hypertension [eg, requiring home oxygen]) | Ineligible to receive myeloablative conditioning | ||
| Kidney disease (eGFR <30 mL/min per 1.73 m2) | Ineligible to receive myeloablative conditioning | ||
| Clinically significant active infection (HIV-1/2, HBV, HCV, HTLV-1/2, tuberculosis, syphilis, toxoplasmosis, Trypanosoma cruzi, or West Nile virus) | Ineligible for transplant until active infection is well controlled | ||
| Cognitive or psychiatric impairment precluding safe therapy and recovery | Ineligible due to inability to comply with transplant precautions | ||
| CNS disease (untreated Moyamoya disease, uncontrolled seizure disorder, or debilitating physical impairment) | Ineligible per trials and/or ineligible to receive myeloablative conditioning | ||
| Other organ dysfunction precluding safe myeloablative conditioning (with busulfan) if not explicitly defined above | Ineligible to receive myeloablative conditioning | ||
| Pregnancy or breastfeeding | Ineligible to receive myeloablative conditioning | ||
| Inability to safety complete therapy (eg, lack of caregiver support, lack of stable housing, and nonadherence with medications, etc) | Patients must be able to attend visits to safely complete the entire process of GT. | ||
| Lack of insurance coverage for GT | A solvent GT program is needed to support patients during and after therapy. | ||
| Listed at other GT programs | Potential unfair advantage over other patients | ||
| Refusing a donor search | To have a complete discussion of alternative therapies, there must be a donor search. Patients may or may not be comfortable undergoing a related donor search for various reasons, but an unrelated donor search should be completed to ensure a full discussion of alternative therapies can be had and to maintain fairness for all patients, including those who may not be able to access allogeneic transplant due to lack of donor availability. This requirement ensures that all patients have the opportunity to explore all viable treatment options. This is also frequently an insurance requirement. | ||
ACS, acute chest syndrome; CCUS, clonal cytopenia of unknown significance; CNS, central nervous system; CVA, cerebrovascular accident; DLCO, diffusing capacity of the lungs for carbon monoxide; eGFR, estimated glomerular filtration rate; exa-cel, exagamglogene autotemcel; HBV, hepatitis B virus; HCV, hepatitis C virus; HSCT, hematopoietic stem cell transplant; HTLV-1/2, human T-lymphotropic virus types 1 and 2; lovo-cel, lovotibeglogene autotemcel; MDS, myelodysplastic syndromes; SpO2, blood oxygen saturation.