Table 3. Theme 3 consensus... | American Society of Hematology

Table 3.

Theme 3 consensus recommendations

JAKi therapy: selection, initiation, and switching	Strength of recommendation,∗ median score (mean score)	Level of consensus†
Q6. What criteria should guide the initiation of JAKi therapy? Do all patients with MF benefit from JAKi treatment? Consensus statement Patients should be assessed with a validated prognostic scoring tool (eg, IPSS, DIPSS, DIPSS Plus, and/or MIPSS70+ version 2.0) and a validated symptom scoring tool (eg, MF-SAF or MPN-SAF TSS). After evaluating risk and symptom burden: JAKi therapy should be considered for all patients with symptomatic splenomegaly, constitutional symptoms, or other disease-related symptoms, regardless of risk status. For transplant-ineligible patients with MF and platelet counts <50 × 10₉/L, momelotinib and pacritinib are the preferred JAKi options, if available. For platelet counts 50 × 10₉/L, management with ruxolitinib, fedratinib, momelotinib, or pacritinib is feasible. For transplant-eligible patients with intermediate-2 or high-risk MF, JAKi therapy may be beneficial before transplantation for controlling the spleen size and/or symptoms, and may improve patient performance status before transplant. Not all patients benefit from JAKi therapy. However, responses to ruxolitinib at the maximum tolerated dose can take up to 6 mo, the RR6 model can be used to evaluate this. Participation in clinical trials is encouraged for all transplant-ineligible patients with MF.	9 (8.76)	n/N = 24/25 (96%)
Q7. What criteria should be used to define JAKi failure and suboptimal response? Consensus statement In clinical practice, JAKi failure may be defined as lack of clinical response, such as spleen or symptom response (ruxolitinib, fedratinib, momelotinib, and pacritinib), or anemia response (momelotinib and pacritinib), when this is the intention of treatment. Suboptimal response may be defined as achieving a clinical response smaller than the treatment goal. Treatment should continue for at least 6 mo before considering JAKi failure or suboptimal response, and a validated symptom scoring tool (eg, MF-SAF or MPN-SAF TSS) should be used to assess treatment response. The RR6 model can also be used to evaluate response to ruxolitinib. However, the degree of intolerance (eg, thrombocytopenia or infections) or toxicity (eg, cardiovascular and thromboembolic events, neurotoxicity, or GI toxicity) may mean JAKi failure or suboptimal response criteria are reached sooner.	9 (8.80)	n/N = 25/25 (100%)
Q8. Which MF parameters (and/or assessment tools) should be used to measure response? When should response assessments be repeated and how often? Consensus statement Spleen size, body weight, and symptoms should be measured monthly to assess clinical responses for the first 3-6 mo, and every 2-3 mo thereafter. For spleen assessment, palpation is recommended; ultrasound and MRI should only be used when clinically required. Symptoms should be evaluated using a validated symptom scoring tool (eg, MF-SAF or MPN-SAF TSS). Repeated evaluation of bone marrow fibrosis and JAK2^V617F allele burden during treatment is not required in clinical practice, but bone marrow aspirate and biopsy should be performed when disease progression is suspected.	9 (8.84)	n/N = 25/25 (100%)
Q9. Is anemia or thrombocytopenia a primary indicator for switching JAKi therapy in patients with MF? Consensus statement Ruxolitinib and fedratinib can both cause treatment-related anemia and thrombocytopenia. For ruxolitinib, an initial drop in Hb levels should be expected and can be managed with add-on therapy (danazol, blood transfusions, IMiDs, or ESAs), if clinically indicated. In patients with worsening anemia and/or thrombocytopenia, a switch to momelotinib or pacritinib (where available) may be considered after 6 mo of ruxolitinib treatment. Where momelotinib and pacritinib are not available, gradual dose reductions of ruxolitinib may be considered (see CS2 and CS4).	9 (8.76)	n/N = 25/25 (100%)
Q10. After JAKi failure, what is the guidance for treatment selection in regions with: Restricted access? Unrestricted access? How should ruxolitinib discontinuation syndrome be managed? Consensus statement In regions with restricted access to other JAKi therapies, a switch from ruxolitinib to fedratinib (where available) or enrollment in a clinical trial is recommended. In regions with unrestricted access, a switch to momelotinib or pacritinib is recommended in patients with anemia or thrombocytopenia. Rechallenging with ruxolitinib after a period without treatment in patients with loss of response is a valid option when alternative JAKi treatments or clinical trials are unavailable. Patients should be monitored for ruxolitinib discontinuation syndrome, regardless of dose and duration of therapy; patients with advanced disease may be at greater risk of discontinuation syndrome. Tapering ruxolitinib dose before discontinuing and adding corticosteroids are recommended. Reintroduction of ruxolitinib may resolve withdrawal symptoms.	9 (8.68)	n/N = 25/25 (100%)

JAKi therapy: selection, initiation, and switching	Strength of recommendation,∗ median score (mean score)	Level of consensus†
Q6. What criteria should guide the initiation of JAKi therapy? Do all patients with MF benefit from JAKi treatment? Consensus statement Patients should be assessed with a validated prognostic scoring tool (eg, IPSS, DIPSS, DIPSS Plus, and/or MIPSS70+ version 2.0) and a validated symptom scoring tool (eg, MF-SAF or MPN-SAF TSS). After evaluating risk and symptom burden: JAKi therapy should be considered for all patients with symptomatic splenomegaly, constitutional symptoms, or other disease-related symptoms, regardless of risk status. For transplant-ineligible patients with MF and platelet counts <50 × 10₉/L, momelotinib and pacritinib are the preferred JAKi options, if available. For platelet counts 50 × 10₉/L, management with ruxolitinib, fedratinib, momelotinib, or pacritinib is feasible. For transplant-eligible patients with intermediate-2 or high-risk MF, JAKi therapy may be beneficial before transplantation for controlling the spleen size and/or symptoms, and may improve patient performance status before transplant. Not all patients benefit from JAKi therapy. However, responses to ruxolitinib at the maximum tolerated dose can take up to 6 mo, the RR6 model can be used to evaluate this. Participation in clinical trials is encouraged for all transplant-ineligible patients with MF.	9 (8.76)	n/N = 24/25 (96%)
Q7. What criteria should be used to define JAKi failure and suboptimal response? Consensus statement In clinical practice, JAKi failure may be defined as lack of clinical response, such as spleen or symptom response (ruxolitinib, fedratinib, momelotinib, and pacritinib), or anemia response (momelotinib and pacritinib), when this is the intention of treatment. Suboptimal response may be defined as achieving a clinical response smaller than the treatment goal. Treatment should continue for at least 6 mo before considering JAKi failure or suboptimal response, and a validated symptom scoring tool (eg, MF-SAF or MPN-SAF TSS) should be used to assess treatment response. The RR6 model can also be used to evaluate response to ruxolitinib. However, the degree of intolerance (eg, thrombocytopenia or infections) or toxicity (eg, cardiovascular and thromboembolic events, neurotoxicity, or GI toxicity) may mean JAKi failure or suboptimal response criteria are reached sooner.	9 (8.80)	n/N = 25/25 (100%)
Q8. Which MF parameters (and/or assessment tools) should be used to measure response? When should response assessments be repeated and how often? Consensus statement Spleen size, body weight, and symptoms should be measured monthly to assess clinical responses for the first 3-6 mo, and every 2-3 mo thereafter. For spleen assessment, palpation is recommended; ultrasound and MRI should only be used when clinically required. Symptoms should be evaluated using a validated symptom scoring tool (eg, MF-SAF or MPN-SAF TSS). Repeated evaluation of bone marrow fibrosis and JAK2^V617F allele burden during treatment is not required in clinical practice, but bone marrow aspirate and biopsy should be performed when disease progression is suspected.	9 (8.84)	n/N = 25/25 (100%)
Q9. Is anemia or thrombocytopenia a primary indicator for switching JAKi therapy in patients with MF? Consensus statement Ruxolitinib and fedratinib can both cause treatment-related anemia and thrombocytopenia. For ruxolitinib, an initial drop in Hb levels should be expected and can be managed with add-on therapy (danazol, blood transfusions, IMiDs, or ESAs), if clinically indicated. In patients with worsening anemia and/or thrombocytopenia, a switch to momelotinib or pacritinib (where available) may be considered after 6 mo of ruxolitinib treatment. Where momelotinib and pacritinib are not available, gradual dose reductions of ruxolitinib may be considered (see CS2 and CS4).	9 (8.76)	n/N = 25/25 (100%)
Q10. After JAKi failure, what is the guidance for treatment selection in regions with: Restricted access? Unrestricted access? How should ruxolitinib discontinuation syndrome be managed? Consensus statement In regions with restricted access to other JAKi therapies, a switch from ruxolitinib to fedratinib (where available) or enrollment in a clinical trial is recommended. In regions with unrestricted access, a switch to momelotinib or pacritinib is recommended in patients with anemia or thrombocytopenia. Rechallenging with ruxolitinib after a period without treatment in patients with loss of response is a valid option when alternative JAKi treatments or clinical trials are unavailable. Patients should be monitored for ruxolitinib discontinuation syndrome, regardless of dose and duration of therapy; patients with advanced disease may be at greater risk of discontinuation syndrome. Tapering ruxolitinib dose before discontinuing and adding corticosteroids are recommended. Reintroduction of ruxolitinib may resolve withdrawal symptoms.	9 (8.68)	n/N = 25/25 (100%)

CS, clinical statement; ESA, erythropoiesis-stimulating agent; GI, gastrointestinal; IPSS, International Prognostic Scoring System; MF-SAF, Myelofibrosis Symptom Assessment Form; MP-SAF, Myeloproliferative Neoplasm Symptom Assessment Form; MRI, magnetic resonance imaging; TSS, Total Symptom Score.

∗

Median score on a 1 to 9 scale (mean score in parentheses).

†

Percentage of votes with 7 to 9 on a 9-point scale. Participants were provided with the voting option “Not Applicable” for recommendations outside their area expertise.

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