There are many ways to slice the “lymphoma pie”. Simplified classification of NHLs Indolent (low...
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Transcript of There are many ways to slice the “lymphoma pie”. Simplified classification of NHLs Indolent (low...
There are many ways to slice the “lymphoma pie”
Simplified classification of NHLs• Indolent (low grade) • Aggressive (intermediate grade) • Highly aggressive (high grade)
• Certain types may not fit cleanly into one of these categories (such as grade 3A follicular lymphoma – can behave as “indolent” in some cases and “aggressive” in others)
• In some cases an indolent lymphoma can “transform” into a more aggressive lymphoma
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Classification of NHL Based on Tumor Behavior
• Indolent NHL– Low grade – Associated with slow disease progression. May not need treatment for years.– Can see prolonged survival even with partial response to therapy– Usually incurable by standard therapy
• FL (gr 1-2), MZL, LPL, SLL Mantle cell? Grade 3A FL?• Aggressive NHL
– Intermediate grade– Rapid growth and may be fatal within months if untreated– Can be cured with intensive therapy– Only patients who achieve complete response are cured
• DLBCL, FL 3B, most T cell NHLs Mantle cell? Grade 3A FL?
• Highly aggressive NHL– High grade– Generally requires treatment within days to weeks– Can be cured with intensive therapy (only if complete response attained)
• Burkitt, Lymphoblastic “Double hit” lymphoma ?
Skarin and Dorfman. CA Cancer J Clin. 1997;47:351.
But nothing is ever that simple…
Some lymphomas don’t fit into one category…
• One type of lymphoma can change into another (transformed)
• Some lymphomas have features of 2 types– “grey zone”: features that
overlap two types– “composite” two different
lymphomas mixed together
How much disease does the patient have?STAGING
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How is the stage of lymphoma determined? Does it matter?
• Stage does matter somewhat in terms of prognosis– However, compared to most other cancers, stage has a much smaller
effect on prognosis– Example: if lung cancer changes from stage I to IV, difference between
curable and not– For HL, stage I-A 90-95% cured with first-line therapy; stage IV-B about 60-
65% cured with first line therapy– For DLBCL, stage I-A 80+ % cured; stage IV-B about 50-60% cured
depending on other factors
• Stage plays a role in selection of treatment, especially for HL and DLBCL
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How is the stage of lymphoma determined? Does it matter?
• Stage does matter somewhat in terms of prognosis– However, compared to most other cancers, stage has a much smaller
effect on prognosis– Example: if lung cancer changes from stage 1 to 4, difference between
curable and not– For HL, stage I-A 90-95% cured with first-line therapy; stage IV-B about 60-
65% cured with first line therapy– For DLBCL, stage I-A 80+ % cured; stage IV-B about 50-60% cured
depending on other factors • Stage plays a role in selection of treatment, especially for HL and DLBCL• For most NHLs, type of lymphoma, prognostic score, and response to
treatment are more important that stage alone
How will the patient do?
PROGNOSIS
Many of the more common lymphomas have unique prognostic scoring systems (DLBCL, FL, MCL, PTCL, CLL/SLL, HL)
For some lymphomas, more sophisticated “molecular” profiling can now identify subtypes (i.e., DLBCL)
Will discuss more in breakout sessions
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How is lymphoma treated?• There is a wide range of treatments• Depends on:
– The type of lymphoma– The goal of treatment– The age and condition of the patient
• In general, surgery is NOT part of the treatment• Treatments are usually
– Chemotherapy– Immunotherapies (rituximab)– Radiation– Novel agents– Blood / marrow transplantation
Conventional chemotherapy
Madagascar rosy periwinkle (vincristine)
First patient ever treated with chemotherapy was a NHL patient in 1942 (nitrogen mustard)Goodman LS et al, JAMA 1946
Castel del MonteConstructed in the 1240s by Emperor Frederick II
In 1950s, a new strain of Streptomyces peucetius isolated – red pigment
Monoclonal antibodies: a special type of protein made by B cells and plasma
cells
Light chain
Heavy chain
Variable region
Antigen binding region
“Targeting” region
“Triggering” region
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Proposed Mechanisms of Action for mAbs
CDCRecruit immune cellsPunch holes in cell
ADCCRecruit immune cells
Apoptosis “direct killing”
Monoclonal antibody therapies
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Brentuximab vedotin
How does radiation work?
• Radiation damages DNA in both normal and malignant cells
• SIZE and DOSE of radiation field affect side effects
• Role of radiation in lymphoma is shifting
“Targeted” therapies
Autologous stem cell transplantation
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Can lymphoma be cured?What does remission mean?When does remission = cure?
Remission versus Cure
Life-threatening
Causing symptoms
No symptoms, but still detectable
Not detectable= REMISSION
Level of Disease
EarlyRelapse
Cure
Time
• All 3 patients started with the same level of disease
LateRelapse
Diagnosis
treatment
• All 3 achieved complete remission• One relapsed early, one relpased late, one was cured• Only time can tell who is who (unless testing improves)• How much time until remission = cure? Is cure even
possible? Depends on the disease and the treatment given
Remission versus Cure
Life-threatening
Causing symptoms
No symptoms, but still detectable
Not detectable= REMISSION
Level of Disease
Cure
Time
Diagnosis
treatment
Highly aggressive1 yr Aggressive
5 yrsIndolent10+ yrs??
Remission = cure when enough time has gone by such that relapse is no longer seen (based on prior studies for type of lymphoma with that treatment)
Lymphoma Overview - Summary• A complex family of blood cancers• A good biopsy (accurate diagnosis) is CRITICAL for
management• We are just beginning to understand why lymphomas
develop• Staging and prognosis are important parts of the overall
management• There are MANY new treatments that are based on better
science
Listen, learn, and ask questions!
SUPPLEMENTAL SLIDES
6/28/06 8/22/06
85 yo F presented with weight loss, weakness, splenomegaly, INR 3.1 (off coumadin). Treated with 4 infusions of Rituxan, with dramatic improvement in energy and PO intake.
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1/25/06 5/14/06
47 yo male, presented with fatigue, night sweats, diffuse bone pains. Biopsy showed Diffuse large B-cell lymphoma
Treated with RCHOP-14 (6 cycles), and 6 intrathecal prophylactic injections (of methotrexate and cytarabine). Achieved complete response.
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1/19/05 1/25/05
23 yo M presented with acute SOB, hypoxia. Found to have supraclav LAD and mediastinal mass Lymphoblastic Lymphoma. Treated with cytoxan, daunorubicin, vincristine, prednisone and L-asparaginase.
Follicular lymphoma (low grade; indolent)
Burkitt lymphoma (highly aggressive; high grade)
Hodgkin lymphoma
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RITs in the Treatment of NHL
90Y Radionuclide
Chelator
Ibritumomab
Tiuxetan
Tositumomab
131I radioisotope