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Three exciting cases that take you to the Discovery Super "G" Detective National Finals!
tutor: Liu Hui; MDT: Yang Yazi, Liu Zhouying
Case summary
Wonderful reviews & questions from experts
tutor: Li Caixia; MDT: Zong Xiangping, Ni Hao, Zhang Bin
Case summary
Wonderful reviews & questions from experts
tutor: Xu Wei; MDT: Liang Jinhua, Chen Wen, Ding Chongyang
Case summary
Wonderful reviews & questions from experts
In order to deeply explore the real-world drug experience of lymphoma, the Discovery Super "G" Detective Project invited many lymphoma multidisciplinary collaboration (MDT) teams in China to conduct in-depth analysis
of real-world cases through case presentations and MDT discussions.
After 6 regional competitions and 3 semi-finals, 8 MDT teams from Yantai Yuhuangding Hospital, Beijing Hospital, Chongqing University Cancer Hospital, Guangxi Medical University Cancer Hospital, Jiangsu Provincial People's Hospital, The First Affiliated Hospital of Soochow University, Qilu Hospital of Shandong University and the First Affiliated Hospital of Xi'an Jiaotong University stood out and were shortlisted for the national finals
.
Recently, the Discovery Super "G" Detective National Finals have successfully come to an end, and Medical Pulse is now sorting out the three award-winning cases as follows for readers
.
tutor: Liu Hui; MDT: Yang Yazi, Liu Zhouying
Professor Yang Yazi of Beijing Hospital shared the clinical diagnosis and treatment process of bridging CAR-T in the treatment of intestinal refractory diffuse large B-cell lymphoma (DLBCL), methodically analyzed the difficulties of this case, and provided a new scheme
for bridging combined with CAR-T for the treatment of refractory DLBCL.
Case summary
The patient was a 43-year-old female who was admitted to the hospital with backache and abdominal distension on 2022-1-14, and was diagnosed with DLBCL (stage IVA, GCB type, aaIPI score 3 points)
after imaging, pathology, FISH and other examinations.
The patient was treated with a 4-course of ZR-CHOP regimen, during which he developed agranulocytosis, persistent gastrointestinal symptoms, gastrointestinal hemorrhage, and Pneumocystis carinii pneumonia (PCP).
After the first 2 courses of treatment, the patient's abdominal pain and bloating were significantly alleviated, and the abdominal circumference was reduced by 6cm, and repeated PET-CT showed partial remission (PR).
PET-CT indicated disease progression (PD)
at the end of 4 courses of treatment.
Considering patients with refractory DLBCL, autologous hematopoietic stem cell transplantation (ASCT) or CAR-T therapy is recommended after salvage therapy, and there is evidence that obinutuzumab plus BTKi is superior to rituximab
.
Treatment with G-DHAP+ zebrutinib regimen was given and stem cells
were collected.
During treatment, patients developed agranulocytosis, thrombocytopenia, severe gastrointestinal reactions, and inability to stop antiemetics
.
Repeat CT showed no significant reduction
of the lesion compared with before.
In the face of refractory and drug-resistant second-line therapy, further CAR-T therapy is considered, but the risk of CAR-T therapy is high, the patient is intestinal involvement and the tumor progresses rapidly, so bridging therapy
is required.
The patient received 2 courses of G-GDP + zebrutinib bridging therapy, and abdominal pelvic CT showed that the lesion was smaller
than before.
After that, CAR-T infusion therapy was performed, and PR
was evaluated after treatment.
*ZR-CHOP: zebrutinib, rituximab, cyclophosphamide, epirubicin, vinpodesine, prednisone; G-DHAP: obinutuzumab, cisplatin, cytarabine, dexamethasone; G-GDP: obinutuzumab, gemcitabine, dexamethasone, cisplatin
Figure 1 CAR-T treatment process
Professor Yang concluded that refractory DLBCL has a poor prognosis, and treatment based on obinutuzumab and BTKi may improve the prognosis and can be used as a bridging treatment for
CAR-T.
CAR-T therapy may be considered for refractory gastrointestinal B-cell lymphoma and is generally safe, but the risk of infection and monitoring for gastrointestinal complications should be noted, particularly in patients with prior perforation or transmural lesions.
Wonderful reviews & questions from experts
Professor Wu Di of the First Affiliated Hospital of Xi'an Jiaotong University, Professor Li Xiaoqiu of the Affiliated Cancer Hospital of Fudan University, and Professor Wang Xuejuan of the Cancer Hospital of the Chinese Academy of Medical Sciences commented that the case belongs to high-risk DLBCL, through chemotherapy, targeted therapy, It is not easy for
CAR-T treatment to achieve good treatment results.
Patients with single-target CAR-T therapy are prone to relapse, and it is necessary to consider the problem of early failure of CAR-T therapy and pay attention to hypermetabolic lesions
that have not been cleared.
At the same time, questions were asked
about the mechanism of BTKi infection, the consideration factors for PET-CT to indicate increased spleen metabolism during treatment, and the correlation between the high expression of BCL-2 and BCL-6 and the SUVmax value of PET-CT.
Professor Yang Yazi of the MDT team said that BTKi can increase the risk of infection in patients by affecting the immune function of B cells, and sulfonamide drugs can prevent PCP infection, but antifungal drugs will affect BTKi drug metabolism, so it is not recommended that patients treated with BTKi receive routine fungal prophylaxis
.
During the treatment of patients, PET-CT can observe the increase in spleen metabolism, which needs to consider the progression of the disease, the use of colony-stimulating factors, hemophagocytic syndrome, and the possibility
of local radiotherapy.
Professor Liu Zhouying said that the high expression of BCL-2 and BCL-6 has a positive correlation with the SUVmax value of PET-CT, but the correlation degree needs to be further
determined.
Click to watch the full replay of this case
tutor: Li Caixia; MDT: Zong Xiangping, Ni Hao, Zhang Bin
Professor Zong Xiangping of the First Affiliated Hospital of Soochow University shared the diagnosis and treatment process of a rare follicular lymphoma (FL) into B lymphoblastic lymphoma/leukemia (B-LBL/ALL), the incidence of FL conversion to B-LBL/ALL in the short term is low, and the clinical diagnosis of B-LBL/ALL is difficult.
This rare and difficult case and the MDT team's innovative diagnosis and treatment process provide new ideas
for clinical diagnosis and treatment.
Case summary
The 65-year-old man, who had cervical lymphadenopathy without obvious causes, was diagnosed with FL (stage IV group A, high-risk) after perfect examination at the local hospital, and was treated with a 6-course RB regimen, and the last PET-CT assessment after 3 courses and 6 courses were all complete remission (CR).
After regular R maintenance therapy every two months, a total of 4 times
.
Two months after the end of maintenance therapy, he presented with weakness in both lower limbs with a proptation of the right eye, and at that time the physical examination of both lower limbs was grade II and incontinence
.
After imaging, examination, and bone marrow examination, B-lbl/all (FL transformation, stage IV group B) was diagnosed, involving bone marrow
.
Ostuzumab + Hyper CVAD A regimen (supplementary dose) 1 course of treatment, zebrutinib + Hyper CVAD B regimen chemotherapy 3 courses of treatment, while taking into account the collection of autologous stem cells and T cells
.
During the treatment, the patient's eye symptoms improved, the muscle strength of the lower limbs gradually returned to normal, the urinary catheter was removed, and PR was evaluated after 3 courses of treatment
.
Considering the high recurrence rate of autologous transplantation and the lack of suitable donors for allogeneic transplantation, autologous transplantation bridging CAR-T therapy was finally selected, and CR was evaluated after 2 months, and BTKi maintenance therapy
was continued.
*RB: rituximab, bendamustine; Hyper CVAD: high-dose cyclophosphamide, vincristine, doxorubicin, dexamethasone alternately with methotrine and cytarabine
Fig.
2 Overall treatment history and efficacy evaluation
Prof.
Zong concluded that FL heterogeneity is strong, the incidence of conversion to B-LBL/ALL is low in the short term, it is highly aggressive, and it is sensitive to strong chemotherapy, but the recurrence rate is extremely high, the prognosis is very poor, and there is no standard treatment plan
.
The addition of small molecule drugs and cellular immunotherapy has improved the disease remission rate, and data from this protocol need to be further accumulated
.
Wonderful reviews & questions from experts
Professor Liu Yao of Chongqing University Cancer Hospital, Professor Liu Weiping of West China Hospital of Sichuan University, and Professor Zhang Shengjian of Fudan University Cancer Hospital It is considered that this case is very rare, and it is difficult to distinguish B-LBL/ALL from high-grade B-cell lymphoma in clinical diagnosis, and it is necessary to further improve relevant examinations to clarify that the lesion cells are precursor B lymphocytes; There is no standard treatment for B-LBL/ALL, and autologous transplantation bridging CAR-T therapy in this case is a very innovative attempt
.
At the same time, the judges asked questions
about the relevant experience of autologous transplantation bridging CAR-T in the treatment of lymphoma in clinical practice and the difficulties of PET-CT in the evaluation of lymphoma efficacy.
Professor Zong Xiangping of the MDT team said that at present, our department is conducting a clinical study using autologous transplantation bridging CAR-T treatment in relapsed/refractory B-cell lymphoma, with a complete response rate (CRR) of about 75%, an objective response rate (ORR) of about 50%, and no complete
statistics on the recurrence rate.
Professor Zhang Bin said that if PET-CT has a new lesion or only a single lesion SUVmax value increases by more than 25% in the follow-up evaluation of lymphoma treatment, clinicians should be reminded to pay attention to the lesion and recommend biopsy to further evaluate the condition
according to pathology.
Click to watch the full replay of this case
Case 31 Case 1 Relapsed/Refractory DLBCL Diagnosis and Treatment Analysis Jiangsu Provincial People's Hospital providedtutor: Xu Wei; MDT: Liang Jinhua, Chen Wen, Ding Chongyang
Professors Liang Jinhua and Chen Wen of Jiangsu Provincial People's Hospital conducted a detailed and in-depth analysis of the diagnosis and treatment process of a relapsed/refractory (R/R) DLBCL patient with primary drug resistance to RTX, which provided a good idea
for the clinical standardized diagnosis and treatment of DLBCL.
Case summary
The patient, a 75-year-old female, was admitted to the hospital in mid-November 2019 for cervical lymphadenopathy and gradually enlarged mass, diagnosed with DLBCL (non-GCB type) in the outer hospital, and CD79a(+), who achieved very good partial remission (VGPR) after 6 courses of first-line standard R-CHOP chemotherapy, and continued 2 courses of PD after chemotherapy; Second-line switch to GemOx + BTKi, assessed for CR followed by BTKi maintenance therapy
.
*R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; GemOx: gemcitabine, oxaliplatin
However, the patient developed a new mass in the neck again within half a year, and was admitted to our department at the end of November 2021, with negative bone marrow routine, pathology, flow cytometry, molecular and chromosome examinations, normal LDH, and PET-CT indicating disease progression (SUVmax=11.
2).
Considering the patient's older age, it progresses repeatedly in the short term; and the lesion is limited to the node; Presenting a relatively indolent clinical process (SUVmax<13), the next treatment option is considered from three points - anti-CD20 monoclonal antibody, chemotherapy drugs, and targeted drugs, for the following reasons: (1) Patients may have RTX resistance, and obinutuzumab can further overcome RTX resistance, so obinutuzumab
is selected.
(2) Considering the patient's physical factors and the recommendations and evidence of NCCN guidelines for third-line therapy, bendamustine was selected as a chemotherapy drug
.
(3) Because the patient has CD79a mutation and there is no more suitable targeted drug
.
Therefore, the patient was given a 4-course GB regimen at the time of third-line salvage therapy, enhanced CT after 2 courses showed CRu, plasma NGS showed minimal residual disease (MRD) negative, and then 2 courses of G monotherapy maintained CRu (Figure 3).
*GB: obinutuzumab + bendamustine
Fig.
3 Evaluation of the efficacy of third-line treatment in GB
Professor Liang concluded that a full understanding of the clinical characteristics and gene expression profile of patients is particularly important for patients to formulate individualized treatment plans, which can help patients achieve sustained deep remission.
Considering that patients are RTX-resistant elderly patients and the clinical process is relatively inert, the GB regimen is one of
the safe and effective regimens that can be considered.
Wonderful reviews & questions from experts
Professor Liu Hui of Beijing Hospital, Professor Wang Xuejuan of Cancer Hospital of Chinese Academy of Medical Sciences, and Professor Li Xiaoqiu of Cancer Hospital of Fudan University believe that the diagnosis and treatment of this case is clear and clear, which provides an excellent example for the clinical diagnosis and treatment of DLBCL.
At the same time, questions were asked
about the correlation between SUVmax value and disease aggressiveness in the diagnosis and treatment of cases, and the PET-CT experience of DLBCL (non-GCB type) patients.
Professor Liang Jinhua of the MDT team said that in most cases, SUVmax value or Ki-67 value and double expression are consistent with the aggressiveness of the disease, and there are occasional cases of low SUVmax and high Ki-67 in clinical practice, which need further research
.
Although there was double expression in this case, SUVmax and Ki-67 were not high, and the course of the disease was relatively inert, so the SUVmax value was consistent
with the aggressiveness.
Professor Ding Chongyang said that DLBCL (non-GCB type) general SUVmax value is relatively high; Based on his own clinical and scientific research experience, Professor Li Xiaoqiu proposed that the SUVmax value of tumor tissues with more active BCR pathway is often higher, and this case is more special, and it is recommended to carry out further pathological testing, especially NGS, to determine the correlation
between molecular typing and efficacy.
Click to watch the full replay of this case
In the Discovery Super "G" Detective National Finals, the MDT teams and judges brought a wonderful academic journey of lymphoma to the majority of blood colleagues in the fierce collision of ideas, and made unremitting efforts
to improve the diagnosis and treatment level of lymphoma in China and promote the process of refinement and standardized diagnosis and treatment of lymphoma in China.
Discovery Super "G" Detective, look forward to seeing you next year!
Execution: Quinta
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