Update points of the guidelines for the diagnosis and treatment of hematological malignancies 2022 CSCO guidelines

From April 23rd to 24th, the 2022 Chinese Society of Clinical Oncology (CSCO) Guidelines Conference was successfully held in a combination of online and offline methods
.

At the meeting, Professor Gong Tiejun from the Harbin Institute of Hematology and Oncology gave a detailed and wonderful explanation on the update points of the "CSCO Guidelines for the Diagnosis and Treatment of Hematological Malignancies" (2022 Edition)
.

The main contents are organized as follows
.

1.
Adult acute lymphoblastic leukemia (ALL) >>>> Burkitt lymphoma/leukemia In view of the WHO classification of hematopoietic and lymphoid tissue tumors, the subtype "Burkitt lymphoma/leukemia" has been classified as mature B lymphocyte tumor.
Guideline updates are no longer incorporated
.

>>>>Cytogenetic examination adds "chromosomal microarray analysis" as level II recommendation
.

>>>>Ph-ALL induction therapy: "CD20 positive patients can be combined with rituximab" is changed to "CD20 positive patients can be combined with anti-CD20 monoclonal antibody"
.

Multi-drug combination chemotherapy regimen: increase the VDCP regimen
.

>>>>Ph+ ALL induction therapy: add "TKI inhibitor + belintauumab"
.

TKI inhibitors: Add the 2nd-generation similar drug flumatinib and the 3rd-generation similar drug Orebatinib
.

Post-remission treatment: Add "For MRD-positive patients, belintuzumab can be used to make MRD-negative bridging allogeneic hematopoietic stem cell transplantation"
.

>>>>
For relapsed and refractory ALLPh-B-ALL, belintuzumab and ogaituzumab are recommended to be adjusted to grade I.

Add "bridging allogeneic hematopoietic stem cell transplantation after achieving remission" as a level I recommendation
.

Ph+ B-ALL recommends belintuzumab and oga-ituzumab as grade II
.

Adjust the recommended level of "chimeric antigen receptor T cell (CAR-T)" therapy to level II
.

2.
Adult (<60 years old) acute myeloid leukemia (AML) (non-acute promyelocytic leukemia [APL]) >>>> prognostic stratification "IDH1, IDH2, DNMT3a" was adjusted from level II recommendation to level I recommendation
.

>>>>Added "extramedullary infiltration (excluding liver, spleen, and lymph node involvement)" for adverse prognostic factors; deleted "chromosomal karyotype or molecular genetic markers associated with poor prognosis; 2 courses of induction chemotherapy failed to achieve complete remission"
.

>>>>Cytogenetic/molecular genetic index risk grading group with poor prognosis increased "t(7;11)(p15;p15)"
.

>>>>Induction remission therapy Class I recommends deleting "Demethoxydaunorubicin (IDA) 12mg/m2, d1~3, cytarabine (Ara-C) 1.
0~2.
0g/m2, q12h, d1, 3, 5 or d1~5"; will "Homoharringtonine (HHT) 2mg/m2, d1~7, DNR 40mg/m2 d1~3, Ara-C 100mg/m2, d1~4, Ara-C 1 ~1.
5g/m2, q12h, d5, 6, 7" was changed to "Homoharringtonine (HHT) 2mg/m2, d1~7, DNR 40mg/m2 d1~3, Ara-C 100mg/m2, d1~ 4.
Ara-C 1g/m2, q12h.
, d5, 6, 7"; "Homoharringtonine (HHT) 2~2.
5mg/m2, d1~7 or 4mg/m2 d1~3, Acclamyces Acla (Acla) 20mg, d1~7, cytarabine (Ara-C) 100~200mg/m2, d1~7" and "Homoharringtonine (HHT) 2~2.
5mg/m2, d1~7 or 4mg/m2 d1~3, daunorubicin (DNR) 40mg/m2, d1~3, cytarabine (Ara-C) 100~200mg/m2, d1~7” was adjusted from level I recommendation to level II recommendation
.

Level II recommends deleting "daunorubicin (DNR) 60~90mg/m2, d1~3, cytarabine (Ara-C) 1.
0~2.
0g/m2, q12h, d1, 3, 5 or d1~5" ; "Homoharringtonine 2~2.
5mg/m2, d1~7, cytarabine (Ara-C) 100~200mg/m2, d1~7", "Daunorubicin (DNR) 45mg/m2, d1~3, cytarabine (Ara-C) 100~200mg/m2, d1~7” was adjusted from the level II recommendation to the level I recommendation
.

>>>>Post-induction therapy monitoring In the post-induction therapy monitoring of high-dose Ara-c regimen, delete the part of "Recheck the bone marrow on the 7th to 14th day"
.

3.
Adult (≥60 years old) AML (non-APL) >>>>Fit patients (1) Fit patients (including no genetic abnormality with poor prognosis; no previous history of blood disease; non-treatment-related AML): Level I recommendation will go to The dose of daunorubicin (IDA) was changed from "8~10mg/m2, d1~3" to "8~12mg/m2, d1~3"
.

Class II recommends deleting "decitabine (20mg/m2/d, 5-10d); azacitidine (75mg/m2/d, 7d)"
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(2) Fit patients (including genetic abnormalities with poor prognosis; previous history of hematological diseases; treatment-related AML): Level I recommendation increases: VEN+AZA/VEN+DEC/VEN+LDAC
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>>>>Increased level I recommendation for Unfit patients: VEN+AZA/VEN+DEC/VEN+LDAC
.

IDH1/IDH2 mutation patients increased: VEN+AZA/DAC (AZA preferred) lvosidenib (IDH1), Enasidenib (IDH2)
.

FLT3 mutation patients increased: priority VEN+AZA, VEN+DAC, AZA/DAC+sorafenib, VEN+LDAC
.

Level II recommendation increases: CD33+ patients: gemtuzumab 6mg/m2 d1, 3mg/m2 d8
.

>>>>Increased level III recommendation for Frail patients: VEN+AZA/VEN+DEC/VEN+LDAC
.

4.
Relapsed and refractory AML (non-APL) >>>> allogeneic hematopoietic stem cell transplantation was adjusted from the recommendation of level III experts to the recommendation of level II experts
.

>>>>For patients with early relapse (<12 months), level III experts recommend adding "VEN+intensive chemotherapy (including FLAG±IDA+VEN, CLAG±IDA+VEN); FLAG-IDA dose reduction for patients ≥60 years old"
.

>>>>In patients with advanced relapse, level III experts recommend adding "VEN+intensive chemotherapy (including FLAG±IDA+VEN, CLAG±IDA+VEN); FLAG-IDA dose reduction for patients ≥60 years old"
.

5.
APL has increased from 14 fusion genes to 16 fusion genes, and the newly added 2 fusion genes are shown in Figure 1
.

Figure 16.
Chronic lymphocytic leukemia (CLL) >>>> newly treated patients with indications for treatment, no del(17p)/TP53 gene mutation, and severe concomitant diseases (CIRS score > 6 points) Level I recommendation: increase " Zanubrutinib"
.

Level II recommendation: add "Obrutinib"
.

Level III recommendation: add "acaltinib"
.

There are treatment indications, no del(17p)/Te53 gene mutation, and no serious concomitant diseases (CIRS score ≤ 6 points) Class I recommendation: add "zanubrutinib"
.

Level II recommendation: add "Obrutinib"
.

Level III recommendation: add "Acalabrutinib, fludarabine + cyclophosphamide + rituximab + BTK inhibitor, bendamustine + rituximab + BTK inhibitor"
.

There are treatment indications and there are del(17p)/TP53 gene mutations.
Class II recommendation: add "obrutinib"
.

Level III recommendation: add "Acalabrutinib"
.

>>>>Relapsed and refractory patients with treatment indications, no del(17p)/TP53 gene mutation, and severe concomitant diseases (CIRS score>6 points) Level II recommendation: add "Acalabrutinib"
.

There are indications for treatment, no del(17p)/Tp53 gene mutation, no serious concomitant diseases (CIRS score ≤ 6 points) Class II recommendation: add "Acalabrutinib"
.

There are treatment indications and there are del(17p)/TP53 gene mutations.
Class II recommendation: add "Acalabrutinib"
.

>>>>The treatment indications for CLL increase "symptomatic organ dysfunction (such as: skin, kidney, lung, etc.
) caused by CLL/SLL"; add "autoimmune hemolytic anemia (AlHA) and/or Immune thrombocytopenia (ITP) poorly responsive to corticosteroids or other standard treatments" to "Autoimmune hemolytic anemia (AlHA) and/or immune thrombocytopenia (ITP) poorly responsive to corticosteroid therapy"
.

7.
Chronic myeloid leukemia (CML) >>>> Pre-treatment evaluation Collect a complete medical history: add "including cardiovascular and cerebrovascular, lung, liver, kidney diseases, etc.
"
.

Risk stratification: Emphasize that "ELTS score is more recognized and used, Sokal score is not suitable for disease prognosis stratification of second-generation TKI as first-line treatment", and the "Hasford" and "EUTOS" score formulas are added
.

>>>>
The first-line treatment was the addition of "flumatinib" .

Advanced patients with T315I resistance and previous TKI therapy: "Orebatinib" and "Clinical Trials" were added
.

Added "Nilotinib should not be the first choice for elderly patients, patients with a history of cardiovascular and cerebrovascular diseases, abnormal glucose and lipid metabolism or liver function" and "Dasatinib should not be the first choice for patients with elderly, pleuropulmonary or pericardial diseases"
.

>>>>Pregnant patients join: (1) Female patients who meet the drug withdrawal criteria can become pregnant after drug withdrawal, or they can plan pregnancy while taking TKI, but the drug needs to be stopped within 5 weeks of pregnancy; (2) Postpartum can be considered Breastfeed for at least 2-10 days
.

If MMR persists, breastfeeding can be extended to restart TKI therapy
.

8.
Multiple myeloma >>>> Diagnostic criteria increased: macrofocal myeloma: there are multiple osteolytic bone destructions on imaging tests, but the proportion of bone marrow plasma cells is <10%, blood and urine M protein The diagnostic criteria for MM were not met
.

>>>>Newly diagnosed multiple myeloma treatment suitable for transplantation (induction therapy) increase: daratumumab + carfilzomib + lenalidomide + dexamethasone (class II)
.

Not suitable for transplantation (induction therapy) increased: daratumumab + lenalidomide + dexamethasone (class I); daratumumab + bortezomib + melphalan + prednisone acetate (I category); melphalan + dexamethasone (category II); delete consolidation and maintenance therapy in this section
.

>>>>Transplantation and consolidation therapy Hematopoietic stem cell transplantation: increase allogeneic hematopoietic stem cell transplantation, young, high-risk patients (category III)
.

Stem cell mobilization: increase G-CSF + plerixafor (class I); etoposide + G-CSF (class I); E-CHOP + G-CSF (class II); cyclophosphamide + G-CSF + plerixa Fu (Class II)
.

>>>> Increased maintenance therapy: daratumumab (class IIA); carfilzomib + lenalidomide (class IIA); daratumumab + lenalidomide (class III)
.

>>>>Supportive treatment of renal insufficiency: emphasizing the value of denosumab and plasma exchange
.

9.
Primary Plasma Cell Leukemia (PPCL) >>>> Diagnostic Criteria The proportion of circulating plasma cells in peripheral blood has been modified from 20% to 5%, and after the modification, it is "proportion of circulating plasma cells in peripheral blood ≥ 5% without definite multiple myeloid" history of cancer"
.

>>>>Induction therapy Newly diagnosed PPCL is suitable for transplantation induction therapy Fit: new participation in clinical trials (class I); proteasome inhibitors (bortezomib/ixazomib) combined with immunomodulators (lenalidomide/ pomalidomide/thalidomide)-based three-drug regimen (category IB)
.

Newly diagnosed PPCL is not suitable for transplantation induction therapy Fit: new participation in clinical trials (class I); proteasome inhibitors (bortezomib/ixazomib) combined with immunomodulators (lenalidomide/pomalidomide/ thalidomide)-based three-drug regimen (category IB)
.

UnFit/frail or Unfit/frail or >75 years old: New: Participate in a clinical trial (category I)
.

>>>>Maintenance therapy added: bortezomib/ixazomib ± lenalidomide-based maintenance therapy is recommended
.

10.
Primary systemic amyloidosis >>>> Pre-treatment evaluation laboratory examination: increase 24-hour urine albumin quantification and urine M protein determination
.

Skeletal examination: Adjust PET-CT to class II
.

Tissue biopsy: increased abdominal fat, hypertrophic tongue, biopsy of involved tissue or organ (heart, kidney) Congo red staining, light chain immunofluorescence analysis, electron microscopy analysis
.

>>>>
Newly diagnosed treatments suitable for transplant increase: daratumumab + bortezomib + dexamethasone (category IA); ixazomib + dexamethasone (category IIA); daratumumab + dexamethasone (Class IIA); Ixazomib + Lenalidomide + Dexamethasone (Class III) .

Not suitable for transplantation increase: melphalan + dexamethasone (category I); bortezomib + lenalidomide + dexamethasone (category III)
.

>>>>Increased treatment for relapse: daratumumab-dexamethasone (class IIA); Bcl-2 inhibitor-dexamethasone (class IIA) >>>> increase in supportive care: such patients are highly prone to Malignant arrhythmia, or even sudden death, should try to avoid or reduce the use of cardiotoxic drugs, and ensure electrolyte balance
.

11.
Waldenström's Macroglobulinemia (WM) >>>> Diagnostic Criteria Delete "WM cannot be ruled out by immunophenotype at this time"
.

>>>>The preferred first-line treatment regimen was revised to "①BR; ②Ibrutinib±R; ③Zanubrutinib monotherapy; ④RCD; ⑤VRd"
.

Other regimens: delete R-CHOP, ibrutinib ±
R.

>>>>The curative effect standard VGPR: Change "the original extramedullary lesions disappeared" to "the original extramedullary lesions shrink"
.

PR: Changed "reduced original extramedullary lesions by ≥50%" to "reduced original extramedullary lesions"
.

12.
Myelodysplastic Syndrome (MDS)>>>>Treatment of del(5q)±1 non-chromosomal anomaly increase Grade III recommends “select appropriate patients for allo-HST”
.

Without del(5q)±other cytogenetic abnormalities, increase the entry of "with RS cells <15% (RS cells <5% with SF3B1 mutation)"; serum EPO concentration ≤500 IU/LI level, it is recommended to delete "+EPO"; increase II Level 3 recommends lenalidomide; Level III recommends adding "clinical trials, select suitable patients for allo-HST"; serum EPO concentration >500IU/L "immunosuppressive therapy" is adjusted to "antithymoglobulin ± cyclosporine"
.

No del(5q) ± other cytogenetic abnormalities with RS cells ≥ 15% (RS cells >

Symptomatic thrombocytopenia or neutropenia is recommended to add "clinical trial" for grade I; for grade II, "eltrombopag, romiprostim" is recommended; for grade III, "clinical trial: select suitable patients for allo-HST" is recommended
.

Symptomatic blasts are recommended for grade II to add "clinical trials; select appropriate patients for allo-HST"; for grade III, "immunomodulatory therapy (thalidomide)" is recommended
.

Suitable candidates for transplantation and suitable donors are recommended to add "iron removal before transplantation" in class II
.

For those who are not suitable for bone marrow transplantation or have no suitable donors for pre-stimulation chemotherapy (CAG, HAG), the recommendation is adjusted from the level I recommendation to the level II recommendation; the "relapse or no response" level I and II recommendation is added
.

13.
Polycythemia vera >>>> Refine the dose of aspirin and interferon and increase the dose of low-dose aspirin to 75-100mg/d
.

Patients with stubborn vasomotor symptoms can increase the dose as appropriate
.

Pegylated proline interferon-α: starting from 250ug/time, 350ug for the second time, and reaching the target dose for the third time, the target dose is 500ug/time, subcutaneous injection, once every 2 weeks
.

14.
Essential thrombocythemia This part is not updated
.

15.
Primary myelofibrosis risk stratification table: increase the GIPSS score
.

Therapeutic Note: Add "ruxolitinib may be used as part of graft-versus-host disease prophylaxis"
.

16.
CD19-CAR-T in the treatment of B-cell malignant tumors (Tribute to Professor Zhou Jianfeng) This part was written by the late Professor Zhou Jianfeng
.

The main update content is as follows: >>>>Indication "relapsed and refractory primary mediastinal large B-cell lymphoma" has been added
.

"Relapsed/refractory after immunochemotherapy and BTK inhibitor therapy" was added before mantle cell lymphoma
.

"Relapsed/refractory after second-line therapy" was added before follicular lymphoma and diffuse large B-cell lymphoma
.

>>>>Increased evaluation before treatment: CMV-DNA, CAR-T clinical studies have observed CMV activation in the myelosuppression phase, which helps to prevent the occurrence of CMV pneumonia and CMV hyperemia
.

>>>>Increase in treatment: the usage and dosage of the listed CAR-T products Akilence injection and Ruikiolance injection
.

>>>>Grading and Management of Inflammatory Factor Release Syndrome (CRS) Increase the use of tocilizumab for grade 1 CRS
.

The timing and frequency of use of grades 2, 3, and 4 CRS corticosteroids were revised
.

>>>> Central nervous system toxicity grading and treatment increase: ICANS is grade 3 and above, and head CT or MRI examination is required
.

>>>>Hypoglobulinemia increases the specific infusion dose "monthly infusion of gamma globulin at 400-500mg/kg"
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Professor Gong Tiejun, Director of the Third Blood Ward, Harbin Institute of Hematology and Oncology, Deputy Chief Physician, Member of the Youth Committee of the Hematology Branch of the Chinese Medical Association, Deputy Director of the Youth Committee of the CSCO Anti-Leukemia and Lymphoma Alliance, Secretary of the Expert Committee of the CSCO Anti-Leukemia Alliance Committee Member Member of the Multiple Myeloma Professional Committee of the Chinese Medical Doctor Association Member of the Histiocyte Disease Professional Committee of the Chinese Medical Doctor Association Member of the Myelology Group of the Hematology and Tumor Committee of the China Anti-Cancer Association Mainly engaged in the clinical work of leukemia and myeloma Editor: Wenting Reviewer: Quinta Typesetting: Wenting Execution: Uni pokes "read the original text", we progress together